Genetic Variant NM_020201.4:c.229G>A (chr17-17303779-G-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1PM2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.90

Publications

0 publications found

Variant links:

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]

NT5M links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NT5M	NM_020201.4	MANE Select	c.229G>A	p.Val77Met	missense	Exon 1 of 5	NP_064586.1	Q9NPB1
NT5M	NM_001438936.1		c.229G>A	p.Val77Met	missense	Exon 1 of 6	NP_001425865.1
NT5M	NM_001438937.1		c.229G>A	p.Val77Met	missense	Exon 1 of 6	NP_001425866.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NT5M	ENST00000389022.9	TSL:1 MANE Select	c.229G>A	p.Val77Met	missense	Exon 1 of 5	ENSP00000373674.4	Q9NPB1
NT5M	ENST00000616989.1	TSL:1	c.229G>A	p.Val77Met	missense	Exon 1 of 5	ENSP00000481269.1	Q2I378
NT5M	ENST00000879604.1		c.229G>A	p.Val77Met	missense	Exon 1 of 6	ENSP00000549663.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.02e-7

AC:

AN:

1423942

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

707384

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30168

American (AMR)

AF:

0.00

AC:

AN:

41910

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25002

East Asian (EAS)

AF:

0.00

AC:

AN:

36360

South Asian (SAS)

AF:

0.00

AC:

AN:

82016

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50234

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5204

European-Non Finnish (NFE)

AF:

9.14e-7

AC:

AN:

1094466

Other (OTH)

AF:

0.00

AC:

AN:

58582

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.065

Eigen

Benign

0.092

Eigen_PC

Benign

-0.042

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.55

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.5

PhyloP100

2.9

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.5

REVEL

Benign

0.24

Sift

Uncertain

0.011

Sift4G

Uncertain

0.054

Polyphen

0.93

Vest4

0.29

MutPred

0.87

Loss of sheet (P = 0.1158)

MVP

0.54

MPC

0.63

ClinPred

0.94

GERP RS

-3.1

PromoterAI

-0.098

Neutral

(source)

Varity_R

0.52

gMVP

0.70

Mutation Taster

=71/29

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over