chr15-34348056-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/22 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14837933).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284292.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUTM1	NM_001284292.2	MANE Select	c.188C>G	p.Ser63Cys	missense	Exon 3 of 8	NP_001271221.2	Q86Y26-4
	NUTM1	NM_001284293.2		c.158C>G	p.Ser53Cys	missense	Exon 2 of 7	NP_001271222.2	Q86Y26-3
	NUTM1	NM_175741.3		c.104C>G	p.Ser35Cys	missense	Exon 3 of 8	NP_786883.2	Q86Y26-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUTM1	ENST00000537011.6	TSL:2 MANE Select	c.188C>G	p.Ser63Cys	missense	Exon 3 of 8	ENSP00000444896.1	Q86Y26-4
	NUTM1	ENST00000333756.5	TSL:1	c.104C>G	p.Ser35Cys	missense	Exon 3 of 8	ENSP00000329448.4	Q86Y26-1
	NUTM1	ENST00000438749.7	TSL:2	c.158C>G	p.Ser53Cys	missense	Exon 2 of 7	ENSP00000407031.3	Q86Y26-3

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111986

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.0
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.079
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.97	D
Vest4		0.23
MutPred		0.22		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
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

hg19: chr15-34640257;