1-155250395-C-T

Variant names:

• chr1-155250395-C-T
• rs1327518406
• NM_006589.3:c.1391G>A

Variant summary

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

The NM_006589.3(ENTREP3):​c.1391G>A​(p.Ser464Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. S464I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENTREP3 NM_006589.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.813
• Publications: 0 publications found

Genes affected

ENTREP3 (HGNC:1233): (endosomal transmembrane epsin interactor 3) This gene is located near the gene for the lysosomal enzyme glucosylceramidase; a deficiency in this enzyme is associated with Gaucher disease. The encoded protein has been identified as a potential binding partner of a WW domain-containing protein which is involved in apoptosis and tumor suppression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

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
ENTREP3	NM_006589.3	c.1391G>A	p.Ser464Asn	missense_variant	Exon 9 of 12	ENST00000361361.7	NP_006580.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENTREP3	ENST00000361361.7	c.1391G>A	p.Ser464Asn	missense_variant	Exon 9 of 12	1	NM_006589.3	ENSP00000354958.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1219388 Hom.: 0 Cov.: 39 AF XY: 0.00 AC XY: 0 AN XY: 605390

African (AFR) AF: 0.00 AC: 0 AN: 26892

American (AMR) AF: 0.00 AC: 0 AN: 30280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21770

East Asian (EAS) AF: 0.00 AC: 0 AN: 32644

South Asian (SAS) AF: 0.00 AC: 0 AN: 74254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44930

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3594

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 934512

Other (OTH) AF: 0.00 AC: 0 AN: 50512

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	.;.;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.57	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	0.81	.;.;L
PhyloP100		0.81
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-0.76	N;N;N
REVEL	Benign	0.088
Sift	Uncertain	0.0020	D;D;D
Sift4G	Benign	0.11	T;T;T
Polyphen		0.98	D;.;D
Vest4		0.35
MutPred		0.18		.;.;Loss of phosphorylation at S464 (P = 0.001);
MVP		0.34
MPC		2.6
ClinPred		0.85	D
GERP RS		4.3
Varity_R		0.23
gMVP		0.21
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.29		Position offset: -7

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1327518406; hg19: chr1-155220186;