rs376662259

Variant names:

• chr3-55950432-T-C
• rs376662259
• NM_015576.3:c.2396A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-55950432-T-C
• chr3-55950432-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015576.3(ERC2):​c.2396A>G​(p.His799Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. H799P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ERC2 NM_015576.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.49
• Publications: 0 publications found

Genes affected

ERC2 (HGNC:31922): (ELKS/RAB6-interacting/CAST family member 2) This gene encodes a protein that belongs to the Rab3-interacting molecule (RIM)-binding protein family. Members of this protein family form part of the cytomatrix at the active zone (CAZ) complex and function as regulators of neurotransmitter release. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17321923).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERC2	NM_015576.3	c.2396A>G	p.His799Arg	missense_variant	Exon 13 of 18	ENST00000288221.11	NP_056391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERC2	ENST00000288221.11	c.2396A>G	p.His799Arg	missense_variant	Exon 13 of 18	1	NM_015576.3	ENSP00000288221.6
ERC2	ENST00000460849.5	n.2396A>G		non_coding_transcript_exon_variant	Exon 13 of 19	1		ENSP00000417445.1
ERC2	ENST00000492584.3	c.2420A>G	p.His807Arg	missense_variant	Exon 13 of 18	5		ENSP00000417280.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461676 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727116

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111854

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Uncertain	0.97
DEOGEN2	Benign	0.064	T;T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.56	.;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.0	L;L
PhyloP100		4.5
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.75	N;.
REVEL	Benign	0.082
Sift	Benign	0.17	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.025	B;B
Vest4		0.29
MutPred		0.39		Gain of MoRF binding (P = 0.0532);Gain of MoRF binding (P = 0.0532);
MVP		0.18
MPC		0.48
ClinPred		0.40	T
GERP RS		6.0
Varity_R		0.27
gMVP		0.63
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs376662259; hg19: chr3-55984460;