rs1555605096

Positions:

• chr17-40628934-T-A
• chr17-40628934-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003079.5(SMARCE1):​c.1087A>T​(p.Thr363Ser) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SMARCE1 NM_003079.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.33

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15228504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCE1	NM_003079.5	c.1087A>T	p.Thr363Ser	missense_variant	11/11	ENST00000348513.12	NP_003070.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCE1	ENST00000348513.12	c.1087A>T	p.Thr363Ser	missense_variant	11/11	1	NM_003079.5	ENSP00000323967	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary cancer-predisposing syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2024

The p.T363S variant (also known as c.1087A>T), located in coding exon 10 of the SMARCE1 gene, results from an A to T substitution at nucleotide position 1087. The threonine at codon 363 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.093	T;.;.;.;T;.;T;.
Eigen	Benign	-0.10
Eigen_PC	Benign	0.081
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.68	.;.;T;D;D;D;D;D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.15	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;.;.;.;L;.;.;.
MutationTaster	Benign	0.99	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.33	N;.;.;.;.;.;N;.
REVEL	Benign	0.026
Sift	Benign	0.11	T;.;.;.;.;.;T;.
Sift4G	Benign	0.50	T;.;.;.;.;.;T;T
Polyphen		0.098	B;.;.;.;B;.;.;.
Vest4		0.31
MutPred		0.15		Loss of glycosylation at S362 (P = 0.1922);.;.;.;Loss of glycosylation at S362 (P = 0.1922);.;.;.;
MVP		0.22
MPC		0.65
ClinPred		0.61	D
GERP RS		4.9
Varity_R		0.066
gMVP		0.057

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: rs1555605096; hg19: chr17-38785186;