dbSNP rs755083086: ENTREP2:p.Thr442Met (chr15-29123634-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015307.2(ENTREP2):c.1325C>T(p.Thr442Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,397,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 0.0000029 ( 0 hom. )

Consequence

ENTREP2
NM_015307.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0570

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04155764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTREP2	NM_015307.2 link	c.1325C>T	p.Thr442Met	missense_variant	Exon 11 of 11	ENST00000261275.5	NP_056122.1	O60320-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENTREP2	ENST00000261275.5 link	c.1325C>T	p.Thr442Met	missense_variant	Exon 11 of 11	5	NM_015307.2	ENSP00000261275.4		O60320-1
ENTREP2	ENST00000560021.1 link	n.1061C>T		non_coding_transcript_exon_variant	Exon 8 of 8	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000646

AC:

AN:

154876

AF XY:

0.0000122

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000167

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000286

AC:

AN:

1397536

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

688882

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31552

American (AMR)

AF:

0.00

AC:

AN:

35632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25166

East Asian (EAS)

AF:

0.00

AC:

AN:

35646

South Asian (SAS)

AF:

0.00

AC:

AN:

79210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49222

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.00000371

AC:

AN:

1077486

Other (OTH)

AF:

0.00

AC:

AN:

57930

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000400

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 03, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1325C>T (p.T442M) alteration is located in exon 11 (coding exon 11) of the FAM189A1 gene. This alteration results from a C to T substitution at nucleotide position 1325, causing the threonine (T) at amino acid position 442 to be replaced by a methionine (M). 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

0.073

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.9

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.0025

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.45

M_CAP

Benign

0.015

MetaRNN

Benign

0.042

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.11

PhyloP100

-0.057

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.98

REVEL

Benign

0.083

Sift

Benign

0.30

Sift4G

Benign

0.33

Polyphen

0.15

Vest4

0.023

MutPred

0.28

Loss of phosphorylation at T442 (P = 0.0049);

MVP

0.030

ClinPred

0.15

GERP RS

-10

Varity_R

0.019

gMVP

0.14

Mutation Taster

=94/6

polymorphism

(source)

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

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rs755083086

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over