22-23833572-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_003073.5(SMARCB1):c.987C>T(p.Ser329Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000843 in 1,614,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

SMARCB1
NM_003073.5 splice_region, synonymous

Scores

Splicing: ADA: 0.00003169

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.205

Publications

0 publications found

Variant links:

Genes affected

SMARCB1 (HGNC:11103): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1) The protein encoded by this gene is part of a complex that relieves repressive chromatin structures, allowing the transcriptional machinery to access its targets more effectively. The encoded nuclear protein may also bind to and enhance the DNA joining activity of HIV-1 integrase. This gene has been found to be a tumor suppressor, and mutations in it have been associated with malignant rhabdoid tumors. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

SMARCB1 Gene-Disease associations (from GenCC):

Coffin-Siris syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
intellectual disability, autosomal dominant 15
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
rhabdoid tumor predisposition syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
SMARCB1-related schwannomatosis
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics
familial multiple meningioma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial rhabdoid tumor
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
schwannomatosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

SMARCB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 22-23833572-C-T is Benign according to our data. Variant chr22-23833572-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 416330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.205 with no splicing effect.

BS2

High AC in GnomAd4 at 61 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCB1	NM_003073.5 link	c.987C>T	p.Ser329Ser	splice_region_variant, synonymous_variant	Exon 8 of 9	ENST00000644036.2	NP_003064.2	Q12824-1
SMARCB1	NM_001362877.2 link	c.1041C>T	p.Ser347Ser	splice_region_variant, synonymous_variant	Exon 8 of 9		NP_001349806.1
SMARCB1	NM_001317946.2 link	c.1014C>T	p.Ser338Ser	splice_region_variant, synonymous_variant	Exon 8 of 9		NP_001304875.1	G5E975Q9H836
SMARCB1	NM_001007468.3 link	c.960C>T	p.Ser320Ser	splice_region_variant, synonymous_variant	Exon 8 of 9		NP_001007469.1	Q12824-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCB1	ENST00000644036.2 link	c.987C>T	p.Ser329Ser	splice_region_variant, synonymous_variant	Exon 8 of 9		NM_003073.5	ENSP00000494049.2		Q12824-1

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000147

AC:

AN:

251474

AF XY:

0.000140

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000513

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00149

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

1112010

Other (OTH)

AF:

0.0000497

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000400

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.00144

AC:

AN:

41584

American (AMR)

AF:

0.0000653

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.000476

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome

Benign:2

Jun 25, 2018

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Feb 03, 2022

Sema4, Sema4

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

- -

SMARCB1-related disorder

Benign:1

Nov 15, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.20

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=71/29

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000032

dbscSNV1_RF

Benign

0.028

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over