Variant 15-29123573-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015307.2(ENTREP2):c.1386A>T(p.Gln462His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ENTREP2
NM_015307.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.52

Variant links:

Genes affected

ENTREP2 (HGNC:29075): (endosomal transmembrane epsin interactor 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENTREP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026846766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENTREP2	NM_015307.2 linkuse as main transcript	c.1386A>T	p.Gln462His	missense_variant	11/11	ENST00000261275.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENTREP2	ENST00000261275.5 linkuse as main transcript	c.1386A>T	p.Gln462His	missense_variant	11/11	5	NM_015307.2	P1	O60320-1
ENTREP2	ENST00000560021.1 linkuse as main transcript	n.1122A>T		non_coding_transcript_exon_variant	8/8	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000129

AC:

AN:

155408

Hom.:

AF XY:

0.0000243

AC XY:

AN XY:

82432

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000183

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1399416

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2024

The c.1386A>T (p.Q462H) alteration is located in exon 11 (coding exon 11) of the FAM189A1 gene. This alteration results from a A to T substitution at nucleotide position 1386, causing the glutamine (Q) at amino acid position 462 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.028

DANN

Benign

0.73

DEOGEN2

Benign

0.0011

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.20

M_CAP

Benign

0.0016

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.51

MutationTaster

Benign

1.0

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.33

REVEL

Benign

0.0060

Sift

Benign

0.57

Sift4G

Benign

0.61

Polyphen

0.0

Vest4

0.038

MutPred

0.17

Gain of glycosylation at T460 (P = 0.0678);

MVP

0.014

ClinPred

0.010

GERP RS

-8.3

Varity_R

0.034

gMVP

0.13

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over