Variant X-129471205-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001282874.2(SMARCA1):c.2564A>G(p.Gln855Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000931 in 1,073,714 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. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.3e-7 ( 0 hom. 0 hem. )

Consequence

SMARCA1
NM_001282874.2 missense, splice_region

Scores

Splicing: ADA: 0.9999

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.81

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 links:

SMARCA1 (HGNC:):

SMARCA1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.759

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCA1	NM_001282874.2 linkuse as main transcript	c.2564A>G	p.Gln855Arg	missense_variant, splice_region_variant	20/25	ENST00000371121.5	NP_001269803.1	B7ZLQ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SMARCA1	ENST00000371121.5 linkuse as main transcript	c.2564A>G	p.Gln855Arg	missense_variant, splice_region_variant	20/25	1	NM_001282874.2	ENSP00000360162.4	B7ZLQ5
SMARCA1	ENST00000371123.5 linkuse as main transcript	c.2528A>G	p.Gln843Arg	missense_variant, splice_region_variant	19/24	1		ENSP00000360164.2	A0A0A0MRP6
SMARCA1	ENST00000371122.8 linkuse as main transcript	c.2564A>G	p.Gln855Arg	missense_variant, splice_region_variant	20/25	1		ENSP00000360163.4	P28370-1
SMARCA1	ENST00000617310.4 linkuse as main transcript	n.2882A>G		splice_region_variant, non_coding_transcript_exon_variant	18/23	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000613

AC:

AN:

163212

Hom.:

AF XY:

0.00

AC XY:

AN XY:

53692

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000814

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.31e-7

AC:

AN:

1073714

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

345890

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000335

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2024

The c.2564A>G (p.Q855R) alteration is located in exon 20 (coding exon 20) of the SMARCA1 gene. This alteration results from a A to G substitution at nucleotide position 2564, causing the glutamine (Q) at amino acid position 855 to be replaced by an arginine (R). 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

Benign

0.24

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.35

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;T;.

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Pathogenic

0.78

MetaRNN

Pathogenic

0.76

D;D;D

MetaSVM

Uncertain

0.78

MutationAssessor

Uncertain

2.3

M;.;.

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-2.3

N;N;D

REVEL

Pathogenic

0.78

Sift

Benign

0.031

D;D;T

Sift4G

Uncertain

0.025

D;D;D

Polyphen

0.67

P;.;P

Vest4

0.67

MutPred

0.57

Gain of MoRF binding (P = 0.0284);.;Gain of MoRF binding (P = 0.0284);

MVP

0.99

MPC

0.98

ClinPred

0.50

GERP RS

5.8

Varity_R

0.87

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.98

SpliceAI score (max)

0.040

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