X-129480789-T-C

Position:

• chrX-129480789-T-C

Variant summary

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

The NM_001282874.2(SMARCA1):​c.2354A>G​(p.Asn785Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000096 in 1,041,950 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.6e-7 (0 hom. 0 hem.)
• Consequence: SMARCA1 NM_001282874.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.14

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 (HGNC:):

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=0.28318048).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCA1	NM_001282874.2	c.2354A>G	p.Asn785Ser	missense_variant	19/25	ENST00000371121.5	NP_001269803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCA1	ENST00000371121.5	c.2354A>G	p.Asn785Ser	missense_variant	19/25	1	NM_001282874.2	ENSP00000360162.4
SMARCA1	ENST00000371123.5	c.2318A>G	p.Asn773Ser	missense_variant	18/24	1		ENSP00000360164.2
SMARCA1	ENST00000371122.8	c.2354A>G	p.Asn785Ser	missense_variant	19/25	1		ENSP00000360163.4
SMARCA1	ENST00000617310.4	n.2672A>G		non_coding_transcript_exon_variant	17/23	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.60e-7 AC: 1 AN: 1041950 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 330568

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: 0.00000122

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

research

HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology

Feb 19, 2021

ACMG codes:PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.057	T;T;.
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Uncertain	-0.020	T
MutationAssessor	Benign	2.0	M;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.4	N;N;.
REVEL	Uncertain	0.33
Sift	Benign	0.31	T;T;.
Sift4G	Benign	0.77	T;T;T
Polyphen		0.0020	B;.;B
Vest4		0.26
MutPred		0.48		Gain of phosphorylation at N785 (P = 0.0388);.;Gain of phosphorylation at N785 (P = 0.0388);
MVP		0.88
MPC		0.48
ClinPred		0.57	D
GERP RS		5.2
Varity_R		0.29
gMVP		0.38

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: rs1933619118; hg19: chrX-128614766;