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 (★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T363A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SMARCE1 NM_003079.5 missense
• Clinical Significance: Not reported in ClinVar
• 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	UniProt
SMARCE1	NM_003079.5	c.1087A>T	p.Thr363Ser	missense_variant	11/11	ENST00000348513.12

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

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
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;