rs12800438

Positions:

• chr11-71459957-G-A
• chr11-71459957-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018161.5(NADSYN1):​c.263+1413G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 152,282 control chromosomes in the GnomAD database, including 27,626 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 0.58 (27592 hom., cov: 34)
  • Exomes 𝑓: 0.68 (34 hom.)
• Consequence: NADSYN1 NM_018161.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46

Genes affected

NADSYN1 (HGNC:29832): (NAD synthetase 1) Nicotinamide adenine dinucleotide (NAD) is a coenzyme in metabolic redox reactions, a precursor for several cell signaling molecules, and a substrate for protein posttranslational modifications. NAD synthetase (EC 6.3.5.1) catalyzes the final step in the biosynthesis of NAD from nicotinic acid adenine dinucleotide (NaAD).[supplied by OMIM, Apr 2004]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NADSYN1	NM_018161.5	c.263+1413G>A		intron_variant		ENST00000319023.7	NP_060631.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NADSYN1	ENST00000319023.7	c.263+1413G>A		intron_variant		1	NM_018161.5	ENSP00000326424	P1

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87468 AN: 152036 Hom.: 27563 Cov.: 34

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.556

GnomAD4 exome AF: 0.680 AC: 87 AN: 128 Hom.: 34 Cov.: 0 AF XY: 0.680 AC XY: 68 AN XY: 100

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.575 AC: 87544 AN: 152154 Hom.: 27592 Cov.: 34 AF XY: 0.559 AC XY: 41573 AN XY: 74356

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.590

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.550

Alfa AF: 0.700 Hom.: 72988

Bravo AF: 0.571

Asia WGS AF: 0.286 AC: 997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.73
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12800438; hg19: chr11-71171003;