Variant 15-34348600-G-C 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_001284292.2(NUTM1):c.732G>C(p.Gln244His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000385 in 1,611,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

NUTM1
NM_001284292.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0550

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 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=0.05379185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NUTM1	NM_001284292.2 linkuse as main transcript	c.732G>C	p.Gln244His	missense_variant	3/8	ENST00000537011.6	NP_001271221.2
NUTM1	NM_001284293.2 linkuse as main transcript	c.702G>C	p.Gln234His	missense_variant	2/7		NP_001271222.2
NUTM1	NM_175741.3 linkuse as main transcript	c.648G>C	p.Gln216His	missense_variant	3/8		NP_786883.2
NUTM1	XM_047432341.1 linkuse as main transcript	c.648G>C	p.Gln216His	missense_variant	3/8		XP_047288297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUTM1	ENST00000537011.6 linkuse as main transcript	c.732G>C	p.Gln244His	missense_variant	3/8	2	NM_001284292.2	ENSP00000444896	A2	Q86Y26-4
NUTM1	ENST00000333756.5 linkuse as main transcript	c.648G>C	p.Gln216His	missense_variant	3/8	1		ENSP00000329448	P2	Q86Y26-1
NUTM1	ENST00000438749.7 linkuse as main transcript	c.702G>C	p.Gln234His	missense_variant	2/7	2		ENSP00000407031	A2	Q86Y26-3

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000443

AC:

AN:

248388

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134524

show subpopulations

Gnomad AFR exome

AF:

0.000687

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:

0.0000185

AC:

AN:

1459766

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

726264

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000230

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.000820

Gnomad4 AMR

AF:

0.0000654

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:

0.000159

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000741

AC:

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

May 28, 2024

The c.648G>C (p.Q216H) alteration is located in exon 2 (coding exon 2) of the NUTM1 gene. This alteration results from a G to C substitution at nucleotide position 648, causing the glutamine (Q) at amino acid position 216 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

0.22

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0081

.;T;.;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.21

T;T;T;.

M_CAP

Benign

0.0064

MetaRNN

Benign

0.054

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N;.;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.1

N;.;N;N

REVEL

Benign

0.050

Sift

Benign

0.039

D;.;D;D

Sift4G

Uncertain

0.013

D;D;D;D

Polyphen

0.20

.;B;.;B

Vest4

0.24

MutPred

0.27

.;Gain of methylation at K221 (P = 0.1346);.;Gain of methylation at K221 (P = 0.1346);

MVP

0.14

MPC

0.065

ClinPred

0.040

GERP RS

2.7

Varity_R

0.092

gMVP

0.21

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