11-71472428-C-T

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.408-21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 1,586,398 control chromosomes in the GnomAD database, including 390,702 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.56 (26472 hom., cov: 33)
  • Exomes 𝑓: 0.69 (364230 hom.)
• Consequence: NADSYN1 NM_018161.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0380

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=-0.82).
• BP6: Variant 11-71472428-C-T is Benign according to our data. Variant chr11-71472428-C-T is described in ClinVar as [Benign]. Clinvar id is 1321838.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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	UniProt
NADSYN1	NM_018161.5	c.408-21C>T		intron_variant		ENST00000319023.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NADSYN1	ENST00000319023.7	c.408-21C>T		intron_variant		1	NM_018161.5	P1

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84636 AN: 151606 Hom.: 26466 Cov.: 33

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.537

GnomAD3 exomes AF: 0.564 AC: 141495 AN: 251066 Hom.: 44225 AF XY: 0.559 AC XY: 75868 AN XY: 135672

Gnomad AFR exome AF: 0.315

Gnomad AMR exome AF: 0.481

Gnomad ASJ exome AF: 0.623

Gnomad EAS exome AF: 0.448

Gnomad SAS exome AF: 0.215

Gnomad FIN exome AF: 0.598

Gnomad NFE exome AF: 0.723

Gnomad OTH exome AF: 0.606

GnomAD4 exome AF: 0.692 AC: 992548 AN: 1434674 Hom.: 364230 Cov.: 29 AF XY: 0.678 AC XY: 485152 AN XY: 715204

Gnomad4 AFR exome AF: 0.300

Gnomad4 AMR exome AF: 0.482

Gnomad4 ASJ exome AF: 0.623

Gnomad4 EAS exome AF: 0.410

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.606

Gnomad4 NFE exome AF: 0.770

Gnomad4 OTH exome AF: 0.637

GnomAD4 genome AF: 0.558 AC: 84661 AN: 151724 Hom.: 26472 Cov.: 33 AF XY: 0.541 AC XY: 40138 AN XY: 74128

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.743

Gnomad4 OTH AF: 0.531

Alfa AF: 0.700 Hom.: 37978

Bravo AF: 0.552

Asia WGS AF: 0.313 AC: 1092 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.2
Dann	Benign	0.65

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: rs2282621; hg19: chr11-71183474; COSMIC: COSV59810150; COSMIC: COSV59810150;