rs555324337

Variant names:

• chr17-17303779-G-A
• rs555324337
• NM_020201.4:c.229G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-17303779-G-A
• chr17-17303779-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_020201.4(NT5M):​c.229G>A​(p.Val77Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,423,942 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. V77L) 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: 2.90

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a binding_site (size 0) in uniprot entity NT5M_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5M	NM_020201.4	c.229G>A	p.Val77Met	missense_variant	Exon 1 of 5	ENST00000389022.9	NP_064586.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5M	ENST00000389022.9	c.229G>A	p.Val77Met	missense_variant	Exon 1 of 5	1	NM_020201.4	ENSP00000373674.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1423942 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 707384

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: 9.14e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.065	T;T
Eigen	Benign	0.092
Eigen_PC	Benign	-0.042
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.5	N;.
REVEL	Benign	0.24
Sift	Uncertain	0.011	D;.
Sift4G	Uncertain	0.054	T;T
Polyphen		0.93	P;P
Vest4		0.29
MutPred		0.87		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP		0.54
MPC		0.63
ClinPred		0.94	D
GERP RS		-3.1
Varity_R		0.52
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs555324337; hg19: chr17-17207093;