rs7636269

Positions:

• chr3-139672326-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001320510.2(NMNAT3):​c.-141+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_001320510.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.571

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NMNAT3	NM_001401600.1	c.-178+5379A>G		intron_variant		ENST00000704800.1	NP_001388529.1
NMNAT3	NR_174944.1	n.268+5379A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NMNAT3	ENST00000704800.1	c.-178+5379A>G		intron_variant			NM_001401600.1	ENSP00000516041	P2
COPB2-DT	ENST00000658348.1	n.1482+88446T>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.512

Gnomad4 OTH AF: 0.465

Alfa AF: 0.489 Hom.: 6342

Bravo AF: 0.446

Asia WGS AF: 0.340 AC: 1182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	7.3
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7636269; hg19: chr3-139391168;