17-17346877-C-G

Variant names:

• chr17-17346877-C-G
• rs754225366
• NM_020201.4:c.617C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020201.4(NT5M):​c.617C>G​(p.Pro206Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000286 in 1,609,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P206L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: NT5M NM_020201.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.20
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19820836).

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.617C>G	p.Pro206Arg	missense	Exon 5 of 5	NP_064586.1	Q9NPB1
	NT5M	NM_001438936.1		c.728C>G	p.Pro243Arg	missense	Exon 6 of 6	NP_001425865.1
	NT5M	NM_001438937.1		c.710C>G	p.Pro237Arg	missense	Exon 6 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.617C>G	p.Pro206Arg	missense	Exon 5 of 5	ENSP00000373674.4	Q9NPB1
	NT5M	ENST00000616989.1	TSL:1	c.635C>G	p.Pro212Arg	missense	Exon 5 of 5	ENSP00000481269.1	Q2I378
	NT5M	ENST00000879604.1		c.710C>G	p.Pro237Arg	missense	Exon 6 of 6	ENSP00000549663.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000204 AC: 5 AN: 244696 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000269

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000295 AC: 43 AN: 1457098 Hom.: 0 Cov.: 31 AF XY: 0.0000290 AC XY: 21 AN XY: 725162

African (AFR) AF: 0.0000299 AC: 1 AN: 33474

American (AMR) AF: 0.0000224 AC: 1 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86244

European-Finnish (FIN) AF: 0.0000204 AC: 1 AN: 48956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.0000288 AC: 32 AN: 1111846

Other (OTH) AF: 0.0000166 AC: 1 AN: 60334

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152176 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74334

African (AFR) AF: 0.0000241 AC: 1 AN: 41450

American (AMR) AF: 0.000131 AC: 2 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000207 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.071	T
Eigen	Benign	-0.051
Eigen_PC	Benign	0.060
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		3.2
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.11
Sift	Benign	0.11	T
Sift4G	Benign	0.11	T
Polyphen		0.047	B
Vest4		0.19
MutPred		0.53		Gain of MoRF binding (P = 0.002)
MVP		0.72
MPC		0.34
ClinPred		0.25	T
GERP RS		4.8
Varity_R		0.53
gMVP		0.44
Mutation Taster		=57/43	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: rs754225366; hg19: chr17-17250191;