Variant 3-47610279-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003074.4(SMARCC1):c.2830A>G(p.Met944Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SMARCC1
NM_003074.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.18

Variant links:

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]

SMARCC1 links:

LOC124906234 (HGNC:):

LOC124906234 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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 link	c.2830A>G	p.Met944Val	missense_variant	26/28	ENST00000254480.10	NP_003065.3	Q92922Q58EY4
LOC124906234	XR_007095902.1 link	n.127-4021T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SMARCC1	ENST00000254480.10 link	c.2830A>G	p.Met944Val	missense_variant	26/28	1	NM_003074.4	ENSP00000254480.5	Q92922
SMARCC1	ENST00000425518.5 link	n.2720A>G		non_coding_transcript_exon_variant	26/28	2
SMARCC1	ENST00000492896.1 link	n.323A>G		non_coding_transcript_exon_variant	2/3	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 07, 2024

The c.2830A>G (p.M944V) alteration is located in exon 26 (coding exon 26) of the SMARCC1 gene. This alteration results from a A to G substitution at nucleotide position 2830, causing the methionine (M) at amino acid position 944 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

0.00032

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Benign

0.69

DEOGEN2

Benign

0.34

Eigen

Benign

-0.080

Eigen_PC

Benign

-0.012

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.32

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.051

Polyphen

0.46

Vest4

0.66

MutPred

0.40

Loss of catalytic residue at M944 (P = 0.0245);

MVP

0.40

MPC

0.46

ClinPred

0.78

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.51

gMVP

0.19

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over