Variant 3-138319575-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001349018.2(NME9):c.98A>C(p.Asp33Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000191 in 1,596,038 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

NME9
NM_001349018.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.01

Variant links:

Genes affected

NME9 (HGNC:21343): (NME/NM23 family member 9) Predicted to enable nucleoside diphosphate kinase activity. Predicted to be involved in nucleotide metabolic process. Predicted to be located in dynein axonemal particle. [provided by Alliance of Genome Resources, Apr 2022]

NME9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NME9	NM_001349018.2 linkuse as main transcript	c.98A>C	p.Asp33Ala	missense_variant	3/11	ENST00000333911.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NME9	ENST00000333911.9 linkuse as main transcript	c.98A>C	p.Asp33Ala	missense_variant	3/11	1	NM_001349018.2	P1	Q86XW9-1

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

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:

0.000220

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000143

AC:

AN:

250960

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135656

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000550

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000181

AC:

261

AN:

1443910

Hom.:

Cov.:

AF XY:

0.000203

AC XY:

146

AN XY:

719452

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.000761

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:

0.000194

Gnomad4 OTH exome

AF:

0.000201

GnomAD4 genome

AF:

0.000289

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.000959

Alfa

AF:

0.000177

Hom.:

Bravo

AF:

0.000389

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.000140

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000415

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.32A>C (p.D11A) alteration is located in exon 5 (coding exon 2) of the NME9 gene. This alteration results from a A to C substitution at nucleotide position 32, causing the aspartic acid (D) at amino acid position 11 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Benign

-0.062

BayesDel_noAF

Uncertain

0.030

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.96

D;.;D;D;D

M_CAP

Benign

0.037

MetaRNN

Uncertain

0.71

D;D;D;D;D

MetaSVM

Uncertain

-0.27

MutationTaster

Benign

0.97

D;D;D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-6.4

D;D;D;D;D

REVEL

Uncertain

0.44

Sift

Uncertain

0.0050

D;D;D;D;D

Sift4G

Uncertain

0.0060

D;D;D;D;D

Polyphen

1.0

D;D;D;D;.

Vest4

0.89

MutPred

0.81

.;.;Loss of phosphorylation at Y35 (P = 0.0979);Loss of phosphorylation at Y35 (P = 0.0979);Loss of phosphorylation at Y35 (P = 0.0979);

MVP

0.48

MPC

0.81

ClinPred

0.85

GERP RS

5.4

Varity_R

0.62

gMVP

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over