chr15-34348358-G-C

Position:

• chr15-34348358-G-C

Variant summary

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

The NM_001284292.2(NUTM1):​c.490G>C​(p.Ala164Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NUTM1 NM_001284292.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.518

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]

ACMG classification

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/exons	MANE	UniProt
NUTM1	NM_001284292.2	c.490G>C	p.Ala164Pro	missense_variant	3/8	ENST00000537011.6
NUTM1	NM_001284293.2	c.460G>C	p.Ala154Pro	missense_variant	2/7
NUTM1	NM_175741.3	c.406G>C	p.Ala136Pro	missense_variant	3/8
NUTM1	XM_047432341.1	c.406G>C	p.Ala136Pro	missense_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUTM1	ENST00000537011.6	c.490G>C	p.Ala164Pro	missense_variant	3/8	2	NM_001284292.2	A2
NUTM1	ENST00000333756.5	c.406G>C	p.Ala136Pro	missense_variant	3/8	1		P2
NUTM1	ENST00000438749.7	c.460G>C	p.Ala154Pro	missense_variant	2/7	2		A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2022

The c.406G>C (p.A136P) 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 406, causing the alanine (A) at amino acid position 136 to be replaced by a proline (P). 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	0.11
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	13
DANN	Uncertain	0.99
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.74	T;T;T;.
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.59	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.9	D;.;D;D
REVEL	Benign	0.19
Sift	Uncertain	0.025	D;.;D;D
Sift4G	Benign	0.081	T;T;T;T
Polyphen		0.41	.;B;.;B
Vest4		0.70
MutPred		0.24		.;Gain of relative solvent accessibility (P = 0.0023);.;Gain of relative solvent accessibility (P = 0.0023);
MVP		0.30
MPC		0.29
ClinPred		0.80	D
GERP RS		0.23
Varity_R		0.36
gMVP		0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-34640559;