rs3794060

Variant names:

• chr11-71476633-C-T
• rs3794060
• NM_018161.5:c.799-1762C>T

Variant summary

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

The NM_018161.5(NADSYN1):​c.799-1762C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 984,538 control chromosomes in the GnomAD database, including 269,239 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 0.53 (25285 hom., cov: 32)
  • Exomes 𝑓: 0.75 (243954 hom.)
• Consequence: NADSYN1 NM_018161.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 63 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.737 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NADSYN1	NM_018161.5	MANE Select	c.799-1762C>T		intron	N/A	NP_060631.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NADSYN1	ENST00000319023.7	TSL:1 MANE Select	c.799-1762C>T		intron	N/A	ENSP00000326424.2	Q6IA69-1
	NADSYN1	ENST00000528509.5	TSL:1	n.*1442C>T		non_coding_transcript_exon	Exon 10 of 10	ENSP00000433472.1	E9PKY6
	NADSYN1	ENST00000528509.5	TSL:1	n.*1442C>T		3_prime_UTR	Exon 10 of 10	ENSP00000433472.1	E9PKY6

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80194 AN: 151800 Hom.: 25281 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.519

GnomAD4 exome AF: 0.755 AC: 628591 AN: 832620 Hom.: 243954 Cov.: 26 AF XY: 0.755 AC XY: 290265 AN XY: 384606

African (AFR) AF: 0.167 AC: 2642 AN: 15774

American (AMR) AF: 0.491 AC: 523 AN: 1066

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 3166 AN: 5144

East Asian (EAS) AF: 0.358 AC: 1304 AN: 3646

South Asian (SAS) AF: 0.218 AC: 3598 AN: 16518

European-Finnish (FIN) AF: 0.586 AC: 177 AN: 302

Middle Eastern (MID) AF: 0.502 AC: 812 AN: 1618

European-Non Finnish (NFE) AF: 0.786 AC: 598223 AN: 761272

Other (OTH) AF: 0.665 AC: 18146 AN: 27280

GnomAD4 genome AF: 0.528 AC: 80207 AN: 151918 Hom.: 25285 Cov.: 32 AF XY: 0.513 AC XY: 38040 AN XY: 74218

African (AFR) AF: 0.221 AC: 9161 AN: 41424

American (AMR) AF: 0.484 AC: 7389 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2135 AN: 3472

East Asian (EAS) AF: 0.382 AC: 1965 AN: 5146

South Asian (SAS) AF: 0.210 AC: 1014 AN: 4818

European-Finnish (FIN) AF: 0.588 AC: 6185 AN: 10520

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.743 AC: 50484 AN: 67964

Other (OTH) AF: 0.513 AC: 1079 AN: 2102

Alfa AF: 0.653 Hom.: 41551

Bravo AF: 0.517

Asia WGS AF: 0.271 AC: 945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.52
DANN	Benign	0.48
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3794060; hg19: chr11-71187679;