Variant 15-29128825-C-T 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.967G>A(p.Gly323Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000636 in 1,550,876 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00063 ( 1 hom. )

Consequence

ENTREP2
NM_015307.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.598

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=0.01273492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENTREP2	NM_015307.2 linkuse as main transcript	c.967G>A	p.Gly323Arg	missense_variant	8/11	ENST00000261275.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENTREP2	ENST00000261275.5 linkuse as main transcript	c.967G>A	p.Gly323Arg	missense_variant	8/11	5	NM_015307.2	P1	O60320-1
ENTREP2	ENST00000560021.1 linkuse as main transcript	n.703G>A		non_coding_transcript_exon_variant	5/8	1

Frequencies

GnomAD3 genomes

AF:

0.000671

AC:

102

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000412

AC:

AN:

155302

Hom.:

AF XY:

0.000376

AC XY:

AN XY:

82408

show subpopulations

Gnomad AFR exome

AF:

0.000885

Gnomad AMR exome

AF:

0.000608

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000184

Gnomad SAS exome

AF:

0.000395

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000488

Gnomad OTH exome

AF:

0.000457

GnomAD4 exome

AF:

0.000633

AC:

885

AN:

1398680

Hom.:

Cov.:

AF XY:

0.000607

AC XY:

419

AN XY:

689830

show subpopulations

Gnomad4 AFR exome

AF:

0.00139

Gnomad4 AMR exome

AF:

0.000588

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000839

Gnomad4 SAS exome

AF:

0.000417

Gnomad4 FIN exome

AF:

0.0000411

Gnomad4 NFE exome

AF:

0.000667

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.000670

AC:

102

AN:

152196

Hom.:

Cov.:

AF XY:

0.000658

AC XY:

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000388

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000491

Hom.:

Bravo

AF:

0.000657

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.000629

AC:

ExAC

AF:

0.000584

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Aug 13, 2021

The c.967G>A (p.G323R) alteration is located in exon 8 (coding exon 8) of the FAM189A1 gene. This alteration results from a G to A substitution at nucleotide position 967, causing the glycine (G) at amino acid position 323 to be replaced by an arginine (R). 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

0.077

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.63

Cadd

Benign

9.9

Dann

Uncertain

1.0

DEOGEN2

Benign

0.0067

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.62

M_CAP

Benign

0.010

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

0.75

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.11

Sift

Benign

0.23

Sift4G

Benign

0.40

Polyphen

0.84

Vest4

0.090

MutPred

0.15

Gain of solvent accessibility (P = 0.0037);

MVP

0.16

ClinPred

0.041

GERP RS

3.4

Varity_R

0.29

gMVP

0.43

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