chr3-47610096-G-A

Position:

• chr3-47610096-G-A

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_003074.4(SMARCC1):​c.3013C>T​(p.Gln1005*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SMARCC1 NM_003074.4 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.66

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]

LOC124906234 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 10 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCC1	NM_003074.4	c.3013C>T	p.Gln1005*	stop_gained	26/28	ENST00000254480.10	NP_003065.3
LOC124906234	XR_007095902.1	n.127-4204G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCC1	ENST00000254480.10	c.3013C>T	p.Gln1005*	stop_gained	26/28	1	NM_003074.4	ENSP00000254480.5
SMARCC1	ENST00000425518.5	n.2903C>T		non_coding_transcript_exon_variant	26/28	2
SMARCC1	ENST00000492896.1	n.506C>T		non_coding_transcript_exon_variant	2/3	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460662 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726642

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

SMARCC1-associated developmental dysgenesis syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Jun 10, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Pathogenic	0.60
CADD	Pathogenic	42
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Uncertain	0.96	D
Vest4		0.64
GERP RS		5.7
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

Publications

LitVar

Other links and lift over

dbSNP: rs2032541460; hg19: chr3-47651586;