17-17303674-A-C

Variant names:

• chr17-17303674-A-C
• rs772697554
• NM_020201.4:c.124A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020201.4(NT5M):​c.124A>C​(p.Met42Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000701 in 1,426,158 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M42I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: NT5M NM_020201.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.79
• Publications: 0 publications found

Genes affected

NT5M (HGNC:15769): (5',3'-nucleotidase, mitochondrial) This gene encodes a 5' nucleotidase that localizes to the mitochondrial matrix. This enzyme dephosphorylates the 5'- and 2'(3')-phosphates of uracil and thymine deoxyribonucleotides. The gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020201.4. 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
	NT5M	NM_020201.4	MANE Select	c.124A>C	p.Met42Leu	missense	Exon 1 of 5	NP_064586.1	Q9NPB1
	NT5M	NM_001438936.1		c.124A>C	p.Met42Leu	missense	Exon 1 of 6	NP_001425865.1
	NT5M	NM_001438937.1		c.124A>C	p.Met42Leu	missense	Exon 1 of 6	NP_001425866.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5M	ENST00000389022.9	TSL:1 MANE Select	c.124A>C	p.Met42Leu	missense	Exon 1 of 5	ENSP00000373674.4	Q9NPB1
	NT5M	ENST00000616989.1	TSL:1	c.124A>C	p.Met42Leu	missense	Exon 1 of 5	ENSP00000481269.1	Q2I378
	NT5M	ENST00000879604.1		c.124A>C	p.Met42Leu	missense	Exon 1 of 6	ENSP00000549663.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1426158 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 709188

African (AFR) AF: 0.00 AC: 0 AN: 29876

American (AMR) AF: 0.00 AC: 0 AN: 41560

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24846

East Asian (EAS) AF: 0.00 AC: 0 AN: 35854

South Asian (SAS) AF: 0.00 AC: 0 AN: 82146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50922

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5524

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1096728

Other (OTH) AF: 0.0000170 AC: 1 AN: 58702

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Benign	0.83
DEOGEN2	Benign	0.092	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.31	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		5.8
PrimateAI	Pathogenic	0.96	D
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.31
Sift	Benign	0.035	D
Sift4G	Uncertain	0.031	D
Polyphen		0.99	D
Vest4		0.60
MutPred		0.76		Loss of catalytic residue at M42 (P = 0.0016)
MVP		0.62
MPC		0.66
ClinPred		0.97	D
GERP RS		2.6
PromoterAI		-0.19	Neutral
Varity_R		0.66
gMVP		0.62
Mutation Taster		=84/16	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

dbSNP: rs772697554; hg19: chr17-17206988;