rs3794060

Positions:

• chr11-71476633-C-T

Variant summary

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

The NM_018161.5(NADSYN1):​c.799-1762C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 984,538 control chromosomes in the GnomAD database, including 269,239 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 (25285 hom., cov: 32)
  • Exomes 𝑓: 0.75 (243954 hom.)
• Consequence: NADSYN1 NM_018161.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NADSYN1	NM_018161.5	c.799-1762C>T		intron_variant		ENST00000319023.7	NP_060631.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NADSYN1	ENST00000319023.7	c.799-1762C>T		intron_variant		1	NM_018161.5	ENSP00000326424	P1

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80194 AN: 151800 Hom.: 25281 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.519

GnomAD4 exome AF: 0.755 AC: 628591 AN: 832620 Hom.: 243954 Cov.: 26 AF XY: 0.755 AC XY: 290265 AN XY: 384606

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.491

Gnomad4 ASJ exome AF: 0.615

Gnomad4 EAS exome AF: 0.358

Gnomad4 SAS exome AF: 0.218

Gnomad4 FIN exome AF: 0.586

Gnomad4 NFE exome AF: 0.786

Gnomad4 OTH exome AF: 0.665

GnomAD4 genome AF: 0.528 AC: 80207 AN: 151918 Hom.: 25285 Cov.: 32 AF XY: 0.513 AC XY: 38040 AN XY: 74218

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.743

Gnomad4 OTH AF: 0.513

Alfa AF: 0.674 Hom.: 32425

Bravo AF: 0.517

Asia WGS AF: 0.271 AC: 945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.52
DANN	Benign	0.48

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: rs3794060; hg19: chr11-71187679;