chr3-47622315-CT-C

Position:

• chr3-47622315-CT-C

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_003074.4(SMARCC1):​c.2672delA​(p.Lys891fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic,risk factor (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMARCC1 NM_003074.4 frameshift
• Clinical Significance: Likely pathogenic; risk factor no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 8.02

Genes affected

SMARCC1 (HGNC:11104): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily c member 1) The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI and contains a predicted leucine zipper motif typical of many transcription factors. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-47622315-CT-C is Pathogenic according to our data. Variant chr3-47622315-CT-C is described in ClinVar as [Likely_pathogenic, risk_factor]. Clinvar id is 684692.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-47622315-CT-C is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCC1	NM_003074.4	c.2672delA	p.Lys891fs	frameshift_variant	25/28	ENST00000254480.10	NP_003065.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCC1	ENST00000254480.10	c.2672delA	p.Lys891fs	frameshift_variant	25/28	1	NM_003074.4	ENSP00000254480.5
SMARCC1	ENST00000425518.5	n.2562delA		non_coding_transcript_exon_variant	25/28	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic; risk factor

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Congenital hydrocephalus Pathogenic:1

Likely pathogenic, no assertion criteria provided

literature only

Yale Center for Mendelian Genomics, Yale University

Jul 05, 2018

- -

Hydrocephalus, congenital, 5, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Feb 15, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1576390243; hg19: chr3-47663805;