NM_003079.5:c.531A>C

Variant names:

• chr17-40635941-T-G
• NM_003079.5:c.531A>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.531A>C​(p.Glu177Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,420,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SMARCE1 NM_003079.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20101762).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCE1	NM_003079.5	c.531A>C	p.Glu177Asp	missense_variant	Exon 7 of 11	ENST00000348513.12	NP_003070.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCE1	ENST00000348513.12	c.531A>C	p.Glu177Asp	missense_variant	Exon 7 of 11	1	NM_003079.5	ENSP00000323967.6
ENSG00000264058	ENST00000476049.1	n.*879A>C		non_coding_transcript_exon_variant	Exon 9 of 13	5		ENSP00000463483.1
ENSG00000264058	ENST00000476049.1	n.*879A>C		3_prime_UTR_variant	Exon 9 of 13	5		ENSP00000463483.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1420372 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 703342

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: 0.0000130

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T;.;.;.;.;.;.;.;.;T;.;.;T;.;.;.;.;.;.;.;.
Eigen	Benign	-0.067
Eigen_PC	Benign	-0.054
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	.;.;D;T;.;D;T;D;D;T;T;.;D;T;D;D;D;D;D;D;D
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.20	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.8	L;.;.;.;L;.;.;.;.;L;.;L;.;.;.;L;.;.;.;.;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-2.3	N;.;.;.;.;.;.;.;N;.;.;.;N;.;.;.;.;.;.;.;.
REVEL	Benign	0.097
Sift	Benign	0.20	T;.;.;.;.;.;.;.;T;.;.;.;T;.;.;.;.;.;.;.;.
Sift4G	Benign	0.18	T;.;.;.;.;T;.;T;T;.;.;.;T;T;.;.;.;.;.;.;.
Polyphen		0.27	B;.;.;.;.;.;.;.;.;B;.;.;B;.;.;.;.;.;.;.;.
Vest4		0.35
MutPred		0.24		Gain of relative solvent accessibility (P = 0.0098);.;.;.;Gain of relative solvent accessibility (P = 0.0098);.;.;.;.;Gain of relative solvent accessibility (P = 0.0098);.;Gain of relative solvent accessibility (P = 0.0098);.;.;.;Gain of relative solvent accessibility (P = 0.0098);.;Gain of relative solvent accessibility (P = 0.0098);.;.;.;
MVP		0.58
MPC		0.69
ClinPred		0.51	D
GERP RS		0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.68
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr17-38792193;