15-34348137-T-A

Position:

• chr15-34348137-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001284292.2(NUTM1):​c.269T>A​(p.Met90Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,892 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NUTM1 NM_001284292.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.92

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24574167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUTM1	NM_001284292.2	c.269T>A	p.Met90Lys	missense_variant	3/8	ENST00000537011.6
NUTM1	NM_001284293.2	c.239T>A	p.Met80Lys	missense_variant	2/7
NUTM1	NM_175741.3	c.185T>A	p.Met62Lys	missense_variant	3/8
NUTM1	XM_047432341.1	c.185T>A	p.Met62Lys	missense_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUTM1	ENST00000537011.6	c.269T>A	p.Met90Lys	missense_variant	3/8	2	NM_001284292.2	A2
NUTM1	ENST00000333756.5	c.185T>A	p.Met62Lys	missense_variant	3/8	1		P2
NUTM1	ENST00000438749.7	c.239T>A	p.Met80Lys	missense_variant	2/7	2		A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 58 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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

Feb 14, 2024

The c.185T>A (p.M62K) alteration is located in exon 2 (coding exon 2) of the NUTM1 gene. This alteration results from a T to A substitution at nucleotide position 185, causing the methionine (M) at amino acid position 62 to be replaced by a lysine (K). 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	0.18
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Benign	0.97
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.44	T;T;T;.
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.99	N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.4	N;.;N;N
REVEL	Benign	0.052
Sift	Uncertain	0.0030	D;.;D;D
Sift4G	Uncertain	0.016	D;D;D;D
Polyphen		0.47	.;P;.;P
Vest4		0.39
MutPred		0.32		.;Gain of ubiquitination at M62 (P = 0.0085);.;Gain of ubiquitination at M62 (P = 0.0085);
MVP		0.46
MPC		0.24
ClinPred		0.70	D
GERP RS		5.7
Varity_R		0.63
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs1031832800; hg19: chr15-34640338;