11-71463507-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.317+22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,608,888 control chromosomes in the GnomAD database, including 49,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6522 hom., cov: 33)
  • Exomes 𝑓: 0.23 (42912 hom.)
• Consequence: NADSYN1 NM_018161.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.14

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=-0.92).
• BP6: Variant 11-71463507-C-T is Benign according to our data. Variant chr11-71463507-C-T is described in ClinVar as [Benign]. Clinvar id is 1321837.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NADSYN1	NM_018161.5	c.317+22C>T		intron_variant		ENST00000319023.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NADSYN1	ENST00000319023.7	c.317+22C>T		intron_variant		1	NM_018161.5	P1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42765 AN: 151934 Hom.: 6525 Cov.: 33

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.316

GnomAD3 exomes AF: 0.286 AC: 70566 AN: 247108 Hom.: 10996 AF XY: 0.292 AC XY: 39129 AN XY: 133864

Gnomad AFR exome AF: 0.343

Gnomad AMR exome AF: 0.226

Gnomad ASJ exome AF: 0.227

Gnomad EAS exome AF: 0.399

Gnomad SAS exome AF: 0.459

Gnomad FIN exome AF: 0.347

Gnomad NFE exome AF: 0.224

Gnomad OTH exome AF: 0.271

GnomAD4 exome AF: 0.225 AC: 328304 AN: 1456836 Hom.: 42912 Cov.: 34 AF XY: 0.233 AC XY: 169108 AN XY: 724868

Gnomad4 AFR exome AF: 0.353

Gnomad4 AMR exome AF: 0.233

Gnomad4 ASJ exome AF: 0.224

Gnomad4 EAS exome AF: 0.457

Gnomad4 SAS exome AF: 0.461

Gnomad4 FIN exome AF: 0.338

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.248

GnomAD4 genome AF: 0.281 AC: 42758 AN: 152052 Hom.: 6522 Cov.: 33 AF XY: 0.294 AC XY: 21808 AN XY: 74302

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.319

Alfa AF: 0.242 Hom.: 1015

Bravo AF: 0.271

Asia WGS AF: 0.371 AC: 1288 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	-0.92
Cadd	Benign	0.048
Dann	Benign	0.56

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: rs1629220; hg19: chr11-71174553; COSMIC: COSV59812176; COSMIC: COSV59812176;