15-34348043-C-G

Variant names:

• chr15-34348043-C-G
• NM_001284292.2:c.175C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001284292.2(NUTM1):​c.175C>G​(p.Leu59Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • 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: 0.380

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 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=0.061537713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUTM1	NM_001284292.2	c.175C>G	p.Leu59Val	missense_variant	Exon 3 of 8	ENST00000537011.6	NP_001271221.2
NUTM1	NM_001284293.2	c.145C>G	p.Leu49Val	missense_variant	Exon 2 of 7		NP_001271222.2
NUTM1	NM_175741.3	c.91C>G	p.Leu31Val	missense_variant	Exon 3 of 8		NP_786883.2
NUTM1	XM_047432341.1	c.91C>G	p.Leu31Val	missense_variant	Exon 3 of 8		XP_047288297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUTM1	ENST00000537011.6	c.175C>G	p.Leu59Val	missense_variant	Exon 3 of 8	2	NM_001284292.2	ENSP00000444896.1
NUTM1	ENST00000333756.5	c.91C>G	p.Leu31Val	missense_variant	Exon 3 of 8	1		ENSP00000329448.4
NUTM1	ENST00000438749.7	c.145C>G	p.Leu49Val	missense_variant	Exon 2 of 7	2		ENSP00000407031.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461854 Hom.: 0 Cov.: 59 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.91C>G (p.L31V) alteration is located in exon 2 (coding exon 2) of the NUTM1 gene. This alteration results from a C to G substitution at nucleotide position 91, causing the leucine (L) at amino acid position 31 to be replaced by a valine (V). 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	0.097
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.4
DANN	Benign	0.86
DEOGEN2	Benign	0.0050	.;T;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.43	T;T;T;.
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.062	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	.;N;.;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.040	N;.;N;N
REVEL	Benign	0.053
Sift	Benign	0.16	T;.;T;T
Sift4G	Benign	0.18	T;T;T;T
Polyphen		0.28	.;B;.;B
Vest4		0.11
MutPred		0.16		.;Loss of catalytic residue at L31 (P = 0.0863);.;Loss of catalytic residue at L31 (P = 0.0863);
MVP		0.19
MPC		0.085
ClinPred		0.32	T
GERP RS		1.6
Varity_R		0.044
gMVP		0.064

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: chr15-34640244;