11-71456403-G-T

Variant names:

• chr11-71456403-G-T
• rs12785878
• NM_018161.5:c.146+1233G>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.146+1233G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 152,022 control chromosomes in the GnomAD database, including 25,588 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 0.54 (25588 hom., cov: 33)
• Consequence: NADSYN1 NM_018161.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 334 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.738 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.146+1233G>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.146+1233G>T		intron	N/A	ENSP00000326424.2	Q6IA69-1
	NADSYN1	ENST00000528509.5	TSL:1	n.146+1233G>T		intron	N/A	ENSP00000433472.1	E9PKY6
	NADSYN1	ENST00000859578.1		c.146+1233G>T		intron	N/A	ENSP00000529637.1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81387 AN: 151902 Hom.: 25585 Cov.: 33

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.535 AC: 81401 AN: 152022 Hom.: 25588 Cov.: 33 AF XY: 0.520 AC XY: 38624 AN XY: 74312

African (AFR) AF: 0.247 AC: 10247 AN: 41442

American (AMR) AF: 0.485 AC: 7416 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2133 AN: 3470

East Asian (EAS) AF: 0.383 AC: 1976 AN: 5156

South Asian (SAS) AF: 0.211 AC: 1016 AN: 4816

European-Finnish (FIN) AF: 0.589 AC: 6220 AN: 10554

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.743 AC: 50528 AN: 67980

Other (OTH) AF: 0.521 AC: 1102 AN: 2116

Alfa AF: 0.670 Hom.: 118320

Bravo AF: 0.525

Asia WGS AF: 0.274 AC: 957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.058
DANN	Benign	0.35
PhyloP100		-0.34
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: rs12785878; hg19: chr11-71167449;