11-71486037-C-T

Variant names:

• chr11-71486037-C-T
• rs10898193
• NM_018161.5:c.1562+389C>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.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
• Publications: 15 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=-0.93).
• 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 rank	MANE	Protein	UniProt
NADSYN1	NM_018161.5	c.1562+389C>T		intron_variant	Intron 16 of 20	ENST00000319023.7	NP_060631.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NADSYN1	ENST00000319023.7	c.1562+389C>T		intron_variant	Intron 16 of 20	1	NM_018161.5	ENSP00000326424.2

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

African (AFR) AF: 0.318 AC: 13198 AN: 41456

American (AMR) AF: 0.258 AC: 3938 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 480 AN: 3468

East Asian (EAS) AF: 0.317 AC: 1639 AN: 5164

South Asian (SAS) AF: 0.337 AC: 1620 AN: 4810

European-Finnish (FIN) AF: 0.284 AC: 2998 AN: 10566

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10919 AN: 67976

Other (OTH) AF: 0.260 AC: 550 AN: 2112

Alfa AF: 0.187 Hom.: 9284

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
PhyloP100		-0.066
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: rs10898193; hg19: chr11-71197083;