chr11-71463507-C-T

Variant names:

• chr11-71463507-C-T
• rs1629220
• NM_018161.5:c.317+22C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018161.5(NADSYN1):​c.317+22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,608,888 control chromosomes in the GnomAD database, including 49,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6522 hom., cov: 33)
  • Exomes 𝑓: 0.23 (42912 hom.)
• Consequence: NADSYN1 NM_018161.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.14
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-71463507-C-T is Benign according to our data. Variant chr11-71463507-C-T is described in ClinVar as Benign. ClinVar VariationId is 1321837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.441 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.317+22C>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.317+22C>T		intron	N/A	ENSP00000326424.2
	NADSYN1	ENST00000528509.5	TSL:1	n.317+22C>T		intron	N/A	ENSP00000433472.1
	NADSYN1	ENST00000859578.1		c.317+22C>T		intron	N/A	ENSP00000529637.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42765 AN: 151934 Hom.: 6525 Cov.: 33

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.316

GnomAD2 exomes AF: 0.286 AC: 70566 AN: 247108 AF XY: 0.292

Gnomad AFR exome AF: 0.343

Gnomad AMR exome AF: 0.226

Gnomad ASJ exome AF: 0.227

Gnomad EAS exome AF: 0.399

Gnomad FIN exome AF: 0.347

Gnomad NFE exome AF: 0.224

Gnomad OTH exome AF: 0.271

GnomAD4 exome AF: 0.225 AC: 328304 AN: 1456836 Hom.: 42912 Cov.: 34 AF XY: 0.233 AC XY: 169108 AN XY: 724868

African (AFR) AF: 0.353 AC: 11763 AN: 33360

American (AMR) AF: 0.233 AC: 10386 AN: 44528

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 5826 AN: 26050

East Asian (EAS) AF: 0.457 AC: 18093 AN: 39586

South Asian (SAS) AF: 0.461 AC: 39615 AN: 86004

European-Finnish (FIN) AF: 0.338 AC: 18000 AN: 53208

Middle Eastern (MID) AF: 0.328 AC: 1887 AN: 5750

European-Non Finnish (NFE) AF: 0.188 AC: 207777 AN: 1108132

Other (OTH) AF: 0.248 AC: 14957 AN: 60218

GnomAD4 genome AF: 0.281 AC: 42758 AN: 152052 Hom.: 6522 Cov.: 33 AF XY: 0.294 AC XY: 21808 AN XY: 74302

African (AFR) AF: 0.338 AC: 14030 AN: 41498

American (AMR) AF: 0.300 AC: 4593 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 762 AN: 3472

East Asian (EAS) AF: 0.397 AC: 2033 AN: 5116

South Asian (SAS) AF: 0.457 AC: 2198 AN: 4808

European-Finnish (FIN) AF: 0.356 AC: 3775 AN: 10594

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14303 AN: 67956

Other (OTH) AF: 0.319 AC: 674 AN: 2114

Alfa AF: 0.242 Hom.: 1015

Bravo AF: 0.271

Asia WGS AF: 0.371 AC: 1288 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Vertebral, cardiac, renal, and limb defects syndrome 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.048
DANN	Benign	0.56
PhyloP100		-2.1
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: rs1629220; hg19: chr11-71174553; COSMIC: COSV59812176; COSMIC: COSV59812176;