Genetic Variant NUTM2E:p.Ala457Asp (chr10-79848531-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001355263.2(NUTM2E):c.1370C>A(p.Ala457Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000091 ( 1 hom., cov: 0)

Exomes 𝑓: 0.00043 ( 85 hom. )

Failed GnomAD Quality Control

Consequence

NUTM2E
NM_001355263.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0290

Variant links:

Genes affected

NUTM2E (HGNC:23448): (NUT family member 2E)

NUTM2E links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00750196).

BP6

Variant 10-79848531-C-A is Benign according to our data. Variant chr10-79848531-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2640648.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUTM2E	NM_001355263.2 link	c.1370C>A	p.Ala457Asp	missense_variant	Exon 8 of 10	ENST00000429984.5	NP_001342192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUTM2E	ENST00000429984.5 link	c.1370C>A	p.Ala457Asp	missense_variant	Exon 8 of 10	5	NM_001355263.2	ENSP00000407521.2		B1AL46
NUTM2E	ENST00000602967.5 link	c.1370C>A	p.Ala457Asp	missense_variant	Exon 5 of 6	5		ENSP00000473558.1		R4GNA6

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

43846

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00254

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000464

AC:

AN:

73248

Hom.:

AF XY:

0.000613

AC XY:

AN XY:

39166

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 SAS exome

AF:

0.00289

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000429

AC:

212

AN:

493648

Hom.:

Cov.:

AF XY:

0.000602

AC XY:

151

AN XY:

250980

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00432

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000413

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000911

AC:

AN:

43892

Hom.:

Cov.:

AF XY:

0.0000922

AC XY:

AN XY:

21688

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00253

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000790

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NUTM2E: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.025

.;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.0047

LIST_S2

Benign

0.40

T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.0075

T;T

MetaSVM

Benign

-0.97

PROVEAN

Uncertain

-3.3

.;D

REVEL

Benign

0.037

Sift

Benign

0.088

.;T

Sift4G

Uncertain

0.053

T;D

Vest4

0.14

MutPred

0.16

Gain of ubiquitination at K456 (P = 0.0212);Gain of ubiquitination at K456 (P = 0.0212);

MVP

0.24

ClinPred

0.077

GERP RS

0.71

Varity_R

0.33

gMVP

0.079

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