NM_001282874.2:c.3082A>G

Variant names:

• chrX-129448392-T-C
• NM_001282874.2:c.3082A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001282874.2(SMARCA1):​c.3082A>G​(p.Met1028Val) variant causes a missense change. 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M1028I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 22)
• Consequence: SMARCA1 NM_001282874.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.22

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28043595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA1	NM_001282874.2	c.3082A>G	p.Met1028Val	missense_variant	Exon 24 of 25	ENST00000371121.5	NP_001269803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA1	ENST00000371121.5	c.3082A>G	p.Met1028Val	missense_variant	Exon 24 of 25	1	NM_001282874.2	ENSP00000360162.4
SMARCA1	ENST00000371123.5	c.3046A>G	p.Met1016Val	missense_variant	Exon 23 of 24	1		ENSP00000360164.2
SMARCA1	ENST00000371122.8	c.3082A>G	p.Met1028Val	missense_variant	Exon 24 of 25	1		ENSP00000360163.4
SMARCA1	ENST00000617310.4	n.3400A>G		non_coding_transcript_exon_variant	Exon 22 of 23	2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3082A>G (p.M1028V) alteration is located in exon 24 (coding exon 24) of the SMARCA1 gene. This alteration results from a A to G substitution at nucleotide position 3082, causing the methionine (M) at amino acid position 1028 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	Benign	0.14
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Benign	0.87
DEOGEN2	Benign	0.043	T;T;.
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Uncertain	0.030	D
MutationAssessor	Benign	1.1	L;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.99	N;N;.
REVEL	Uncertain	0.34
Sift	Benign	0.28	T;T;.
Sift4G	Benign	0.30	T;T;T
Polyphen		0.026	B;.;B
Vest4		0.39
MutPred		0.35		Loss of helix (P = 0.028);.;Loss of helix (P = 0.028);
MVP		0.87
MPC		0.67
ClinPred		0.48	T
GERP RS		5.9
Varity_R		0.41
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-128582369;