rs7636269

Variant names:

• chr3-139672326-T-C
• rs7636269
• NM_001401600.1:c.-178+5379A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001401600.1(NMNAT3):​c.-178+5379A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,056 control chromosomes in the GnomAD database, including 16,357 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 0.46 (16357 hom., cov: 32)
• Consequence: NMNAT3 NM_001401600.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.571
• Publications: 13 publications found

Genes affected

NMNAT3 (HGNC:20989): (nicotinamide nucleotide adenylyltransferase 3) This gene encodes a member of the nicotinamide/nicotinic acid mononucleotide adenylyltransferase family. These enzymes use ATP to catalyze the synthesis of nicotinamide adenine dinucleotide or nicotinic acid adenine dinucleotide from nicotinamide mononucleotide or nicotinic acid mononucleotide, respectively. The encoded protein is localized to mitochondria and may also play a neuroprotective role as a molecular chaperone. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

COPB2-DT (HGNC:55579): (COPB2 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001401600.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMNAT3	NM_001401600.1	MANE Select	c.-178+5379A>G		intron	N/A	NP_001388529.1	Q96T66-1
	NMNAT3	NM_001320510.2		c.-141+5379A>G		intron	N/A	NP_001307439.1	A0A2R8YFG2
	NMNAT3	NM_001401598.1		c.-138+5379A>G		intron	N/A	NP_001388527.1	A0A2R8YFG2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMNAT3	ENST00000704800.1	MANE Select	c.-178+5379A>G		intron	N/A	ENSP00000516041.1	Q96T66-1
	NMNAT3	ENST00000339837.9	TSL:1	c.-103+5379A>G		intron	N/A	ENSP00000340523.5	Q96T66-2
	NMNAT3	ENST00000506254.5	TSL:1	n.-141+5379A>G		intron	N/A	ENSP00000423335.1	D6R975

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69683 AN: 151938 Hom.: 16354 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.466

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.458 AC: 69712 AN: 152056 Hom.: 16357 Cov.: 32 AF XY: 0.452 AC XY: 33603 AN XY: 74312

African (AFR) AF: 0.413 AC: 17094 AN: 41424

American (AMR) AF: 0.398 AC: 6087 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1651 AN: 3468

East Asian (EAS) AF: 0.229 AC: 1188 AN: 5186

South Asian (SAS) AF: 0.453 AC: 2182 AN: 4820

European-Finnish (FIN) AF: 0.476 AC: 5034 AN: 10574

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.512 AC: 34816 AN: 67976

Other (OTH) AF: 0.465 AC: 982 AN: 2112

Alfa AF: 0.489 Hom.: 7353

Bravo AF: 0.446

Asia WGS AF: 0.340 AC: 1182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	7.3
DANN	Benign	0.79
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7636269; hg19: chr3-139391168;