11-71463406-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018161.5(NADSYN1):c.264-26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 1,604,516 control chromosomes in the GnomAD database, including 397,031 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (27351 hom., cov: 31)
  • Exomes 𝑓: 0.69 (369680 hom.)
• Consequence: NADSYN1 NM_018161.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.48

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 11-71463406-A-G is Benign according to our data. Variant chr11-71463406-A-G is described in ClinVar as [Benign]. Clinvar id is 1321836.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NADSYN1	NM_018161.5	c.264-26A>G		intron_variant		ENST00000319023.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NADSYN1	ENST00000319023.7	c.264-26A>G		intron_variant		1	NM_018161.5	P1

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86830 AN: 151830 Hom.: 27323 Cov.: 31

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.553

GnomAD3 exomes AF: 0.563 AC: 140738 AN: 249914 Hom.: 44076 AF XY: 0.558 AC XY: 75409 AN XY: 135116

Gnomad AFR exome AF: 0.368

Gnomad AMR exome AF: 0.484

Gnomad ASJ exome AF: 0.621

Gnomad EAS exome AF: 0.387

Gnomad SAS exome AF: 0.213

Gnomad FIN exome AF: 0.600

Gnomad NFE exome AF: 0.724

Gnomad OTH exome AF: 0.602

GnomAD4 exome AF: 0.693 AC: 1006308 AN: 1452568 Hom.: 369680 Cov.: 30 AF XY: 0.679 AC XY: 491068 AN XY: 723176

Gnomad4 AFR exome AF: 0.346

Gnomad4 AMR exome AF: 0.485

Gnomad4 ASJ exome AF: 0.622

Gnomad4 EAS exome AF: 0.346

Gnomad4 SAS exome AF: 0.220

Gnomad4 FIN exome AF: 0.607

Gnomad4 NFE exome AF: 0.771

Gnomad4 OTH exome AF: 0.637

GnomAD4 genome AF: 0.572 AC: 86906 AN: 151948 Hom.: 27351 Cov.: 31 AF XY: 0.556 AC XY: 41268 AN XY: 74256

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.546

Alfa AF: 0.695 Hom.: 37760

Bravo AF: 0.567

Asia WGS AF: 0.285 AC: 995 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Vertebral, cardiac, renal, and limb defects syndrome 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.0070
Dann	Benign	0.27
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2276362; hg19: chr11-71174452; COSMIC: COSV59812675; COSMIC: COSV59812675;