rs771308672

Variant names:

• chr17-40636060-C-G
• rs771308672
• NM_003079.5:c.412G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-40636060-C-G
• chr17-40636060-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A138T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SMARCE1 NM_003079.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.79
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• familial meningioma

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, G2P, Ambry Genetics
• Coffin-Siris syndrome 5

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Coffin-Siris syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial multiple meningioma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000264058 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 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	c.412G>C	p.Ala138Pro	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.412G>C	p.Ala138Pro	missense_variant	Exon 7 of 11	1	NM_003079.5	ENSP00000323967.6
ENSG00000264058	ENST00000476049.1	n.*760G>C		non_coding_transcript_exon_variant	Exon 9 of 13	5		ENSP00000463483.1
ENSG00000264058	ENST00000476049.1	n.*760G>C		3_prime_UTR_variant	Exon 9 of 13	5		ENSP00000463483.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460420 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726414

African (AFR) AF: 0.00 AC: 0 AN: 33404

American (AMR) AF: 0.00 AC: 0 AN: 44462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 85808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111478

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome Cov.: 32

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	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
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	D
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	D
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	T
MutationAssessor	Uncertain	2.6	M;.;.;.;M;.;.;.;.;M;.;M;.;.;.;M;.;.;.;.;.
PhyloP100		4.8
PrimateAI	Pathogenic	0.79	T
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	D
GERP RS		5.6
Varity_R		0.89
gMVP		0.95
Mutation Taster		=9/91	disease causing

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

Other links and lift over

dbSNP: rs771308672; hg19: chr17-38792312;