15-34348056-C-G

Variant names:

• chr15-34348056-C-G
• NM_001284292.2:c.188C>G

Variant summary

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

The NM_001284292.2(NUTM1):​c.188C>G​(p.Ser63Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,868 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: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: NUTM1 NM_001284292.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.99

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=0.14837933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUTM1	NM_001284292.2	c.188C>G	p.Ser63Cys	missense_variant	Exon 3 of 8	ENST00000537011.6	NP_001271221.2
NUTM1	NM_001284293.2	c.158C>G	p.Ser53Cys	missense_variant	Exon 2 of 7		NP_001271222.2
NUTM1	NM_175741.3	c.104C>G	p.Ser35Cys	missense_variant	Exon 3 of 8		NP_786883.2
NUTM1	XM_047432341.1	c.104C>G	p.Ser35Cys	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.188C>G	p.Ser63Cys	missense_variant	Exon 3 of 8	2	NM_001284292.2	ENSP00000444896.1
NUTM1	ENST00000333756.5	c.104C>G	p.Ser35Cys	missense_variant	Exon 3 of 8	1		ENSP00000329448.4
NUTM1	ENST00000438749.7	c.158C>G	p.Ser53Cys	missense_variant	Exon 2 of 7	2		ENSP00000407031.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461868 Hom.: 0 Cov.: 58 AF XY: 0.00 AC XY: 0 AN XY: 727240

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.104C>G (p.S35C) 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 104, causing the serine (S) at amino acid position 35 to be replaced by a cysteine (C). 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	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.0070	.;T;.;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.48	T;T;T;.
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	.;N;.;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.6	N;.;N;N
REVEL	Benign	0.079
Sift	Uncertain	0.0090	D;.;D;D
Sift4G	Uncertain	0.0050	D;D;D;D
Polyphen		0.97	.;D;.;D
Vest4		0.23
MutPred		0.22		.;Loss of phosphorylation at S35 (P = 0.0028);.;Loss of phosphorylation at S35 (P = 0.0028);
MVP		0.34
MPC		0.32
ClinPred		0.43	T
GERP RS		3.8
Varity_R		0.14
gMVP		0.15

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: chr15-34640257;