11-71486037-C-T

Position:

• chr11-71486037-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.1562+389C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,046 control chromosomes in the GnomAD database, including 4,667 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 0.23 (4667 hom., cov: 32)
• Consequence: NADSYN1 NM_018161.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NADSYN1	NM_018161.5	c.1562+389C>T		intron_variant		ENST00000319023.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NADSYN1	ENST00000319023.7	c.1562+389C>T		intron_variant		1	NM_018161.5	P1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35606 AN: 151928 Hom.: 4650 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.257

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.235 AC: 35657 AN: 152046 Hom.: 4667 Cov.: 32 AF XY: 0.245 AC XY: 18207 AN XY: 74322

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.260

Alfa AF: 0.175 Hom.: 5203

Bravo AF: 0.232

Asia WGS AF: 0.312 AC: 1083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.7
DANN	Benign	0.63

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: rs10898193; hg19: chr11-71197083;