3-138314339-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001349018.2(NME9):c.453G>A(p.Glu151=) 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, single submitter B:1
• Conservation: PhyloP100: -0.362

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

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 3-138314339-C-T is Benign according to our data. Variant chr3-138314339-C-T is described in ClinVar as [Benign]. Clinvar id is 403245.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
NME9	NM_001349018.2	c.453G>A	p.Glu151=	synonymous_variant	6/11	ENST00000333911.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NME9	ENST00000333911.9	c.453G>A	p.Glu151=	synonymous_variant	6/11	1	NM_001349018.2	P1

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

GnomAD3 exomes AF: 0.722 AC: 179599 AN: 248842 Hom.: 65582 AF XY: 0.716 AC XY: 96319 AN XY: 134556

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 SAS exome AF: 0.672

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

Gnomad4 AFR exome AF: 0.579

Gnomad4 AMR exome AF: 0.846

Gnomad4 ASJ exome AF: 0.649

Gnomad4 EAS exome AF: 0.833

Gnomad4 SAS exome AF: 0.669

Gnomad4 FIN exome AF: 0.713

Gnomad4 NFE exome AF: 0.718

Gnomad4 OTH exome AF: 0.706

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

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.796

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.822

Gnomad4 SAS AF: 0.681

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.706

Gnomad4 OTH AF: 0.686

Alfa AF: 0.698 Hom.: 26581

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	1.8
Dann	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs9289556; hg19: chr3-138033181;