X-129471267-C-G

Position:

• chrX-129471267-C-G

Variant summary

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

The NM_001282874.2(SMARCA1):​c.2502G>C​(p.Lys834Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: SMARCA1 NM_001282874.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.65

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 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
SMARCA1	NM_001282874.2	c.2502G>C	p.Lys834Asn	missense_variant	20/25	ENST00000371121.5	NP_001269803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCA1	ENST00000371121.5	c.2502G>C	p.Lys834Asn	missense_variant	20/25	1	NM_001282874.2	ENSP00000360162.4
SMARCA1	ENST00000371123.5	c.2466G>C	p.Lys822Asn	missense_variant	19/24	1		ENSP00000360164.2
SMARCA1	ENST00000371122.8	c.2502G>C	p.Lys834Asn	missense_variant	20/25	1		ENSP00000360163.4
SMARCA1	ENST00000617310.4	n.2820G>C		non_coding_transcript_exon_variant	18/23	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 09, 2024

The c.2502G>C (p.K834N) alteration is located in exon 20 (coding exon 20) of the SMARCA1 gene. This alteration results from a G to C substitution at nucleotide position 2502, causing the lysine (K) at amino acid position 834 to be replaced by an asparagine (N). 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	Pathogenic	0.67
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T;.
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Pathogenic	0.82	D
MutationAssessor	Pathogenic	3.3	M;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.9	D;D;.
REVEL	Pathogenic	0.67
Sift	Uncertain	0.027	D;D;.
Sift4G	Uncertain	0.046	D;T;D
Polyphen		0.99	D;.;D
Vest4		0.56
MutPred		0.47		Loss of ubiquitination at K834 (P = 6e-04);.;Loss of ubiquitination at K834 (P = 6e-04);
MVP		0.92
MPC		1.6
ClinPred		0.99	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.91
gMVP		0.73

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-128605244;