3-138306554-A-G

Variant names:

• chr3-138306554-A-G
• rs9846480
• NM_001349018.2:c.461-74T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349018.2(NME9):​c.461-74T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 835,438 control chromosomes in the GnomAD database, including 156,709 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.53 (23360 hom., cov: 33)
  • Exomes 𝑓: 0.62 (133349 hom.)
• Consequence: NME9 NM_001349018.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205
• Publications: 21 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349018.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME9	NM_001349018.2	MANE Select	c.461-74T>C		intron	N/A	NP_001335947.1
	NME9	NM_001349024.2		c.344-74T>C		intron	N/A	NP_001335953.1
	NME9	NM_001349025.2		c.344-74T>C		intron	N/A	NP_001335954.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NME9	ENST00000333911.9	TSL:1 MANE Select	c.461-74T>C		intron	N/A	ENSP00000335444.3
	NME9	ENST00000492993.5	TSL:1	n.278-74T>C		intron	N/A	ENSP00000419355.1
	NME9	ENST00000317876.8	TSL:5	c.278-74T>C		intron	N/A	ENSP00000321929.4

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79813 AN: 151940 Hom.: 23352 Cov.: 33

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.545

GnomAD4 exome AF: 0.615 AC: 420342 AN: 683382 Hom.: 133349 AF XY: 0.609 AC XY: 219858 AN XY: 360878

African (AFR) AF: 0.230 AC: 4059 AN: 17672

American (AMR) AF: 0.780 AC: 26255 AN: 33660

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 10173 AN: 16896

East Asian (EAS) AF: 0.830 AC: 29750 AN: 35844

South Asian (SAS) AF: 0.511 AC: 30041 AN: 58756

European-Finnish (FIN) AF: 0.629 AC: 31380 AN: 49866

Middle Eastern (MID) AF: 0.504 AC: 1942 AN: 3852

European-Non Finnish (NFE) AF: 0.616 AC: 266623 AN: 432910

Other (OTH) AF: 0.593 AC: 20119 AN: 33926

GnomAD4 genome AF: 0.525 AC: 79842 AN: 152056 Hom.: 23360 Cov.: 33 AF XY: 0.532 AC XY: 39562 AN XY: 74326

African (AFR) AF: 0.244 AC: 10134 AN: 41472

American (AMR) AF: 0.689 AC: 10541 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2138 AN: 3472

East Asian (EAS) AF: 0.826 AC: 4269 AN: 5168

South Asian (SAS) AF: 0.525 AC: 2530 AN: 4818

European-Finnish (FIN) AF: 0.624 AC: 6597 AN: 10572

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.615 AC: 41816 AN: 67948

Other (OTH) AF: 0.544 AC: 1148 AN: 2112

Alfa AF: 0.597 Hom.: 118850

Bravo AF: 0.524

Asia WGS AF: 0.649 AC: 2259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.6
DANN	Benign	0.69
PhyloP100		0.20
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: rs9846480; hg19: chr3-138025396;