Genetic Variant NUTM1:p.Glu240Ala (chr15-34348587-A-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001284292.2(NUTM1):c.719A>C(p.Glu240Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,612,990 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NUTM1
NM_001284292.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.14

Variant links:

Genes affected

NUTM1 (HGNC:29919): (NUT midline carcinoma family member 1) Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NUTM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 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
NUTM1	NM_001284292.2 link	c.719A>C	p.Glu240Ala	missense_variant	Exon 3 of 8	ENST00000537011.6	NP_001271221.2	Q86Y26-4
NUTM1	NM_001284293.2 link	c.689A>C	p.Glu230Ala	missense_variant	Exon 2 of 7		NP_001271222.2	Q86Y26-3
NUTM1	NM_175741.3 link	c.635A>C	p.Glu212Ala	missense_variant	Exon 3 of 8		NP_786883.2	Q86Y26-1
NUTM1	XM_047432341.1 link	c.635A>C	p.Glu212Ala	missense_variant	Exon 3 of 8		XP_047288297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NUTM1	ENST00000537011.6 link	c.719A>C	p.Glu240Ala	missense_variant	Exon 3 of 8	2	NM_001284292.2	ENSP00000444896.1	Q86Y26-4
NUTM1	ENST00000333756.5 link	c.635A>C	p.Glu212Ala	missense_variant	Exon 3 of 8	1		ENSP00000329448.4	Q86Y26-1
NUTM1	ENST00000438749.7 link	c.689A>C	p.Glu230Ala	missense_variant	Exon 2 of 7	2		ENSP00000407031.3	Q86Y26-3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249506

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

135008

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000205

AC:

AN:

1460782

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726714

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.635A>C (p.E212A) alteration is located in exon 2 (coding exon 2) of the NUTM1 gene. This alteration results from a A to C substitution at nucleotide position 635, causing the glutamic acid (E) at amino acid position 212 to be replaced by an alanine (A). 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

0.22

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.058

.;T;.;T

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.92

D;D;D;.

M_CAP

Benign

0.040

MetaRNN

Uncertain

0.63

D;D;D;D

MetaSVM

Benign

-0.66

MutationAssessor

Pathogenic

3.1

.;M;.;M

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.8

D;.;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.0080

D;.;D;D

Sift4G

Uncertain

0.0070

D;D;D;D

Polyphen

1.0

.;D;.;D

Vest4

0.79

MutPred

0.28

.;Loss of ubiquitination at K208 (P = 0.0421);.;Loss of ubiquitination at K208 (P = 0.0421);

MVP

0.53

MPC

0.42

ClinPred

0.96

GERP RS

5.7

Varity_R

0.65

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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