chrX-129465529-C-A

Variant names:

• chrX-129465529-C-A
• NM_001282874.2:c.3021G>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001282874.2(SMARCA1):​c.3021G>T​(p.Arg1007Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R1007R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: SMARCA1 NM_001282874.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.948

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA1	NM_001282874.2	c.3021G>T	p.Arg1007Ser	missense_variant	Exon 23 of 25	ENST00000371121.5	NP_001269803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA1	ENST00000371121.5	c.3021G>T	p.Arg1007Ser	missense_variant	Exon 23 of 25	1	NM_001282874.2	ENSP00000360162.4
SMARCA1	ENST00000371123.5	c.2985G>T	p.Arg995Ser	missense_variant	Exon 22 of 24	1		ENSP00000360164.2
SMARCA1	ENST00000371122.8	c.3021G>T	p.Arg1007Ser	missense_variant	Exon 23 of 25	1		ENSP00000360163.4
SMARCA1	ENST00000617310.4	n.3339G>T		non_coding_transcript_exon_variant	Exon 21 of 23	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.45
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T;T;.
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Pathogenic	1.0	D;D;D
M_CAP	Pathogenic	0.66	D
MetaRNN	Pathogenic	0.95	D;D;D
MetaSVM	Pathogenic	0.86	D
MutationAssessor	Pathogenic	3.9	H;.;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-5.4	D;D;.
REVEL	Pathogenic	0.90
Sift	Pathogenic	0.0	D;D;.
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.74
MutPred		0.86		Loss of MoRF binding (P = 0.0371);.;Loss of MoRF binding (P = 0.0371);
MVP		0.98
MPC		1.7
ClinPred		1.0	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.96
gMVP		0.97

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-128599506;