rs972863493

Variant names:

• chr22-23801076-C-A
• rs972863493
• NM_003073.5:c.495C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-23801076-C-A
• chr22-23801076-C-G
• chr22-23801076-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_003073.5(SMARCB1):​c.495C>A​(p.Pro165Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P165P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMARCB1 NM_003073.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.96
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 22-23801076-C-A is Benign according to our data. Variant chr22-23801076-C-A is described in CliVar as Likely_benign. Clinvar id is 2826991.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23801076-C-A is described in CliVar as Likely_benign. Clinvar id is 2826991.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23801076-C-A is described in CliVar as Likely_benign. Clinvar id is 2826991.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23801076-C-A is described in CliVar as Likely_benign. Clinvar id is 2826991.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23801076-C-A is described in CliVar as Likely_benign. Clinvar id is 2826991.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23801076-C-A is described in CliVar as Likely_benign. Clinvar id is 2826991.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23801076-C-A is described in CliVar as Likely_benign. Clinvar id is 2826991.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23801076-C-A is described in CliVar as Likely_benign. Clinvar id is 2826991.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23801076-C-A is described in CliVar as Likely_benign. Clinvar id is 2826991.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23801076-C-A is described in CliVar as Likely_benign. Clinvar id is 2826991.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23801076-C-A is described in CliVar as Likely_benign. Clinvar id is 2826991.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23801076-C-A is described in CliVar as Likely_benign. Clinvar id is 2826991.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23801076-C-A is described in CliVar as Likely_benign. Clinvar id is 2826991.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23801076-C-A is described in CliVar as Likely_benign. Clinvar id is 2826991.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23801076-C-A is described in CliVar as Likely_benign. Clinvar id is 2826991.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23801076-C-A is described in CliVar as Likely_benign. Clinvar id is 2826991.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23801076-C-A is described in CliVar as Likely_benign. Clinvar id is 2826991.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23801076-C-A is described in CliVar as Likely_benign. Clinvar id is 2826991.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23801076-C-A is described in CliVar as Likely_benign. Clinvar id is 2826991.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23801076-C-A is described in CliVar as Likely_benign. Clinvar id is 2826991.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23801076-C-A is described in CliVar as Likely_benign. Clinvar id is 2826991.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-23801076-C-A is described in CliVar as Likely_benign. Clinvar id is 2826991.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.96 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCB1	NM_003073.5	c.495C>A	p.Pro165Pro	synonymous_variant	Exon 4 of 9	ENST00000644036.2	NP_003064.2
SMARCB1	NM_001362877.2	c.495C>A	p.Pro165Pro	synonymous_variant	Exon 4 of 9		NP_001349806.1
SMARCB1	NM_001317946.2	c.468C>A	p.Pro156Pro	synonymous_variant	Exon 4 of 9		NP_001304875.1
SMARCB1	NM_001007468.3	c.468C>A	p.Pro156Pro	synonymous_variant	Exon 4 of 9		NP_001007469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCB1	ENST00000644036.2	c.495C>A	p.Pro165Pro	synonymous_variant	Exon 4 of 9		NM_003073.5	ENSP00000494049.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 06, 2023

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	-0.38
CADD	Benign	4.8
DANN	Benign	0.84
PhyloP100		-3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs972863493; hg19: chr22-24143263;