11-71472691-T-C

Variant names:

• chr11-71472691-T-C
• rs2282618
• NM_018161.5:c.459+191T>C

Variant summary

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

The NM_018161.5(NADSYN1):​c.459+191T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 152,202 control chromosomes in the GnomAD database, including 55,504 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 0.84 (55504 hom., cov: 33)
• Consequence: NADSYN1 NM_018161.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NADSYN1	NM_018161.5	c.459+191T>C		intron_variant	Intron 6 of 20	ENST00000319023.7	NP_060631.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NADSYN1	ENST00000319023.7	c.459+191T>C		intron_variant	Intron 6 of 20	1	NM_018161.5	ENSP00000326424.2

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128488 AN: 152084 Hom.: 55507 Cov.: 33

Gnomad AFR AF: 0.675

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.838

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.945

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.954

Gnomad OTH AF: 0.857

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

GnomAD4 genome AF: 0.844 AC: 128508 AN: 152202 Hom.: 55504 Cov.: 33 AF XY: 0.841 AC XY: 62561 AN XY: 74398

African (AFR) AF: 0.674 AC: 27953 AN: 41500

American (AMR) AF: 0.795 AC: 12173 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.838 AC: 2909 AN: 3472

East Asian (EAS) AF: 0.842 AC: 4331 AN: 5144

South Asian (SAS) AF: 0.671 AC: 3235 AN: 4820

European-Finnish (FIN) AF: 0.945 AC: 10033 AN: 10612

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.954 AC: 64918 AN: 68030

Other (OTH) AF: 0.855 AC: 1803 AN: 2110

Alfa AF: 0.866 Hom.: 3304

Bravo AF: 0.827

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.24
DANN	Benign	0.54
PhyloP100		-1.8
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: rs2282618; hg19: chr11-71183737;