3-138314339-C-T

Variant names:

• chr3-138314339-C-T
• rs9289556
• NM_001349018.2:c.453G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001349018.2(NME9):​c.453G>A​(p.Glu151Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 1,596,882 control chromosomes in the GnomAD database, including 408,924 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.69 (36091 hom., cov: 32)
  • Exomes 𝑓: 0.72 (372833 hom.)
• Consequence: NME9 NM_001349018.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.362
• Publications: 20 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.05).
• BP6: Variant 3-138314339-C-T is Benign according to our data. Variant chr3-138314339-C-T is described in ClinVar as Benign. ClinVar VariationId is 403245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.362 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NME9	NM_001349018.2	c.453G>A	p.Glu151Glu	synonymous_variant	Exon 6 of 11	ENST00000333911.9	NP_001335947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NME9	ENST00000333911.9	c.453G>A	p.Glu151Glu	synonymous_variant	Exon 6 of 11	1	NM_001349018.2	ENSP00000335444.3

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104171 AN: 151964 Hom.: 36070 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.688

GnomAD2 exomes AF: 0.722 AC: 179599 AN: 248842 AF XY: 0.716

Gnomad AFR exome AF: 0.580

Gnomad AMR exome AF: 0.855

Gnomad ASJ exome AF: 0.653

Gnomad EAS exome AF: 0.819

Gnomad FIN exome AF: 0.713

Gnomad NFE exome AF: 0.708

Gnomad OTH exome AF: 0.713

GnomAD4 exome AF: 0.717 AC: 1035350 AN: 1444800 Hom.: 372833 Cov.: 27 AF XY: 0.714 AC XY: 514044 AN XY: 719666

African (AFR) AF: 0.579 AC: 19127 AN: 33038

American (AMR) AF: 0.846 AC: 37298 AN: 44102

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 16866 AN: 25984

East Asian (EAS) AF: 0.833 AC: 32893 AN: 39472

South Asian (SAS) AF: 0.669 AC: 57093 AN: 85392

European-Finnish (FIN) AF: 0.713 AC: 38067 AN: 53364

Middle Eastern (MID) AF: 0.593 AC: 3408 AN: 5744

European-Non Finnish (NFE) AF: 0.718 AC: 788361 AN: 1097868

Other (OTH) AF: 0.706 AC: 42237 AN: 59836

GnomAD4 genome AF: 0.685 AC: 104242 AN: 152082 Hom.: 36091 Cov.: 32 AF XY: 0.690 AC XY: 51308 AN XY: 74348

African (AFR) AF: 0.593 AC: 24575 AN: 41476

American (AMR) AF: 0.796 AC: 12168 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2266 AN: 3472

East Asian (EAS) AF: 0.822 AC: 4258 AN: 5180

South Asian (SAS) AF: 0.681 AC: 3279 AN: 4816

European-Finnish (FIN) AF: 0.704 AC: 7449 AN: 10578

Middle Eastern (MID) AF: 0.634 AC: 185 AN: 292

European-Non Finnish (NFE) AF: 0.706 AC: 48017 AN: 67976

Other (OTH) AF: 0.686 AC: 1444 AN: 2106

Alfa AF: 0.699 Hom.: 29455

Bravo AF: 0.691

Asia WGS AF: 0.744 AC: 2589 AN: 3478

EpiCase AF: 0.703

EpiControl AF: 0.694

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.8
DANN	Benign	0.41
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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: rs9289556; hg19: chr3-138033181; COSMIC: COSV108153416;