17-40630845-C-T

Variant names:

• chr17-40630845-C-T
• NM_003079.5:c.896G>A

Variant summary

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

The NM_003079.5(SMARCE1):​c.896G>A​(p.Arg299Lys) 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMARCE1 NM_003079.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.03

Genes affected

SMARCE1 (HGNC:11109): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily e, member 1) The protein encoded by this gene is part of the large ATP-dependent chromatin remodeling complex SWI/SNF, which is required for transcriptional activation of genes normally repressed by chromatin. The encoded protein, either alone or when in the SWI/SNF complex, can bind to 4-way junction DNA, which is thought to mimic the topology of DNA as it enters or exits the nucleosome. The protein contains a DNA-binding HMG domain, but disruption of this domain does not abolish the DNA-binding or nucleosome-displacement activities of the SWI/SNF complex. Unlike most of the SWI/SNF complex proteins, this protein has no yeast counterpart. [provided by RefSeq, Jul 2008]

ENSG00000264058 (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=0.29696876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCE1	NM_003079.5	c.896G>A	p.Arg299Lys	missense_variant	Exon 10 of 11	ENST00000348513.12	NP_003070.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCE1	ENST00000348513.12	c.896G>A	p.Arg299Lys	missense_variant	Exon 10 of 11	1	NM_003079.5	ENSP00000323967.6
ENSG00000264058	ENST00000476049.1	n.*1244G>A		non_coding_transcript_exon_variant	Exon 12 of 13	5		ENSP00000463483.1
ENSG00000264058	ENST00000476049.1	n.*1244G>A		3_prime_UTR_variant	Exon 12 of 13	5		ENSP00000463483.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary cancer-predisposing syndrome Uncertain:1

Feb 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.R299K variant (also known as c.896G>A), located in coding exon 9 of the SMARCE1 gene, results from a G to A substitution at nucleotide position 896. The arginine at codon 299 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.12	T;.;.;.;.;.;.;.;.;T;.;.;T;.;.;.;.;.;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.69	.;.;T;T;.;T;T;T;T;T;T;.;T;T;T;T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.30	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.;.;.;L;.;.;.;.;L;.;L;.;.;.;L;.;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.0	N;.;.;.;.;.;.;.;N;.;.;.;N;.;.;.;.;.;.
REVEL	Benign	0.12
Sift	Benign	0.049	D;.;.;.;.;.;.;.;T;.;.;.;T;.;.;.;.;.;.
Sift4G	Benign	0.28	T;.;.;.;.;T;.;T;T;.;.;.;T;T;.;.;.;.;.
Polyphen		0.96	P;.;.;.;.;.;.;.;.;P;.;.;.;.;.;.;.;.;.
Vest4		0.59
MutPred		0.27		Gain of ubiquitination at R299 (P = 0.0054);.;.;.;Gain of ubiquitination at R299 (P = 0.0054);.;.;.;.;Gain of ubiquitination at R299 (P = 0.0054);.;Gain of ubiquitination at R299 (P = 0.0054);.;.;.;Gain of ubiquitination at R299 (P = 0.0054);.;Gain of ubiquitination at R299 (P = 0.0054);.;
MVP		0.44
MPC		0.91
ClinPred		0.62	D
GERP RS		5.5
Varity_R		0.35
gMVP		0.14

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: chr17-38787097;