11-71483513-G-A

Variant names:

• chr11-71483513-G-A
• rs3829251
• NM_018161.5:c.1319+496G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018161.5(NADSYN1):​c.1319+496G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,164 control chromosomes in the GnomAD database, including 3,802 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 0.21 (3802 hom., cov: 33)
• Consequence: NADSYN1 NM_018161.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201
• Publications: 103 publications found

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]

NADSYN1 Gene-Disease associations (from GenCC):

• vertebral, cardiac, renal, and limb defects syndrome 3

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• congenital vertebral-cardiac-renal anomalies syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018161.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NADSYN1	NM_018161.5	MANE Select	c.1319+496G>A		intron	N/A	NP_060631.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NADSYN1	ENST00000319023.7	TSL:1 MANE Select	c.1319+496G>A		intron	N/A	ENSP00000326424.2
	NADSYN1	ENST00000530055.5	TSL:2	c.206+496G>A		intron	N/A	ENSP00000431820.1
	NADSYN1	ENST00000529840.5	TSL:5	c.206+496G>A		intron	N/A	ENSP00000437172.1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32461 AN: 152046 Hom.: 3797 Cov.: 33

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.213 AC: 32482 AN: 152164 Hom.: 3802 Cov.: 33 AF XY: 0.224 AC XY: 16632 AN XY: 74370

African (AFR) AF: 0.246 AC: 10208 AN: 41498

American (AMR) AF: 0.249 AC: 3811 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3472

East Asian (EAS) AF: 0.314 AC: 1622 AN: 5168

South Asian (SAS) AF: 0.337 AC: 1624 AN: 4818

European-Finnish (FIN) AF: 0.283 AC: 2999 AN: 10588

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.160 AC: 10907 AN: 68002

Other (OTH) AF: 0.244 AC: 514 AN: 2110

Alfa AF: 0.177 Hom.: 12086

Bravo AF: 0.208

Asia WGS AF: 0.305 AC: 1060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.69
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3829251; hg19: chr11-71194559;