rs769981337

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001282874.2(SMARCA1):c.3053C>T(p.Thr1018Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000929 in 1,076,952 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.3e-7 ( 0 hom. 0 hem. )

Consequence

SMARCA1
NM_001282874.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.87

Publications

0 publications found

Variant links:

Genes affected

SMARCA1 (HGNC:11097): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 1) This gene encodes a member of the SWI/SNF family of proteins. The encoded protein is an ATPase which is expressed in diverse tissues and contributes to the chromatin remodeling complex that is involved in transcription. The protein may also play a role in DNA damage, growth inhibition and apoptosis of cancer cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

SMARCA1 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Ambry Genetics
X-linked intellectual disability
Inheritance: XL Classification: LIMITED Submitted by: ClinGen
schizophrenia
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

SMARCA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.914

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282874.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMARCA1	NM_001282874.2	MANE Select	c.3053C>T	p.Thr1018Ile	missense	Exon 24 of 25	NP_001269803.1	B7ZLQ5
SMARCA1	NM_001282875.2		c.3017C>T	p.Thr1006Ile	missense	Exon 23 of 24	NP_001269804.1	A0A0A0MRP6
SMARCA1	NM_003069.5		c.3053C>T	p.Thr1018Ile	missense	Exon 24 of 25	NP_003060.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMARCA1	ENST00000371121.5	TSL:1 MANE Select	c.3053C>T	p.Thr1018Ile	missense	Exon 24 of 25	ENSP00000360162.4	B7ZLQ5
SMARCA1	ENST00000371123.5	TSL:1	c.3017C>T	p.Thr1006Ile	missense	Exon 23 of 24	ENSP00000360164.2	A0A0A0MRP6
SMARCA1	ENST00000371122.8	TSL:1	c.3053C>T	p.Thr1018Ile	missense	Exon 24 of 25	ENSP00000360163.4	P28370-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000113

AC:

AN:

177479

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000249

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.29e-7

AC:

AN:

1076952

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

344496

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25834

American (AMR)

AF:

0.00

AC:

AN:

33809

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19107

East Asian (EAS)

AF:

0.00

AC:

AN:

30005

South Asian (SAS)

AF:

0.00

AC:

AN:

51812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40186

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4068

European-Non Finnish (NFE)

AF:

0.00000121

AC:

AN:

826776

Other (OTH)

AF:

0.00

AC:

AN:

45355

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.39

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

M_CAP

Pathogenic

0.81

MetaRNN

Pathogenic

0.91

MetaSVM

Pathogenic

0.98

MutationAssessor

Pathogenic

3.5

PhyloP100

8.9

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-5.4

REVEL

Pathogenic

0.88

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.039

Polyphen

1.0

Vest4

0.72

MutPred

0.71

Loss of phosphorylation at T1018 (P = 0.0223)

MVP

0.98

MPC

1.6

ClinPred

0.98

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.87

gMVP

0.82

Mutation Taster

=40/60

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over