Genetic Variant NM_003079.5:c.412G>C (chr17-40636060-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_003079.5(SMARCE1):c.412G>C(p.Ala138Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,420 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SMARCE1
NM_003079.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.79

Variant links:

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]

SMARCE1 links:

ENSG00000264058 (HGNC:):

ENSG00000264058 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
SMARCE1	NM_003079.5 link	c.412G>C	p.Ala138Pro	missense_variant	Exon 7 of 11	ENST00000348513.12	NP_003070.3	Q969G3-1A0A024R1S7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SMARCE1	ENST00000348513.12 link	c.412G>C	p.Ala138Pro	missense_variant	Exon 7 of 11	1	NM_003079.5	ENSP00000323967.6	Q969G3-1
ENSG00000264058	ENST00000476049.1 link	n.*760G>C		non_coding_transcript_exon_variant	Exon 9 of 13	5		ENSP00000463483.1
ENSG00000264058	ENST00000476049.1 link	n.*760G>C		3_prime_UTR_variant	Exon 9 of 13	5		ENSP00000463483.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460420

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726414

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

D;.;.;.;.;.;.;.;.;D;.;.;T;.;.;.;.;.;.;T;.

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

.;.;D;D;.;D;D;D;D;D;D;.;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.56

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.32

MutationAssessor

Uncertain

2.6

M;.;.;.;M;.;.;.;.;M;.;M;.;.;.;M;.;.;.;.;.

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-4.9

D;.;.;.;.;.;.;.;D;.;.;.;D;.;.;.;.;.;.;.;.

REVEL

Benign

0.26

Sift

Uncertain

0.0050

D;.;.;.;.;.;.;.;D;.;.;.;D;.;.;.;.;.;.;.;.

Sift4G

Uncertain

0.0050

D;.;.;.;.;D;.;D;D;.;.;.;D;D;.;.;.;.;.;.;.

Polyphen

0.97

D;.;.;.;.;.;.;.;.;D;.;.;D;.;.;.;.;.;.;.;.

Vest4

0.81

MutPred

0.25

Gain of glycosylation at A138 (P = 0.0621);.;.;.;Gain of glycosylation at A138 (P = 0.0621);.;.;.;.;Gain of glycosylation at A138 (P = 0.0621);.;Gain of glycosylation at A138 (P = 0.0621);.;.;.;Gain of glycosylation at A138 (P = 0.0621);.;Gain of glycosylation at A138 (P = 0.0621);.;.;.;

MVP

0.40

MPC

1.5

ClinPred

0.97

GERP RS

5.6

Varity_R

0.89

gMVP

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over