11-71464128-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_018161.5(NADSYN1):c.393G>A(p.Pro131=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,610,078 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (7 hom.)
• Consequence: NADSYN1 NM_018161.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.65

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 11-71464128-G-A is Benign according to our data. Variant chr11-71464128-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3025011.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.65 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NADSYN1	NM_018161.5	c.393G>A	p.Pro131=	synonymous_variant	5/21	ENST00000319023.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NADSYN1	ENST00000319023.7	c.393G>A	p.Pro131=	synonymous_variant	5/21	1	NM_018161.5	P1

Frequencies

GnomAD3 genomes AF: 0.00160 AC: 243 AN: 152250 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.0114

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000970

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00174 AC: 422 AN: 242214 Hom.: 1 AF XY: 0.00176 AC XY: 230 AN XY: 130974

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00112

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00172

Gnomad SAS exome AF: 0.000410

Gnomad FIN exome AF: 0.0108

Gnomad NFE exome AF: 0.00102

Gnomad OTH exome AF: 0.00167

GnomAD4 exome AF: 0.00106 AC: 1540 AN: 1457710 Hom.: 7 Cov.: 30 AF XY: 0.00103 AC XY: 743 AN XY: 724608

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.00113

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00134

Gnomad4 SAS exome AF: 0.000376

Gnomad4 FIN exome AF: 0.0105

Gnomad4 NFE exome AF: 0.000703

Gnomad4 OTH exome AF: 0.000996

GnomAD4 genome AF: 0.00160 AC: 244 AN: 152368 Hom.: 1 Cov.: 32 AF XY: 0.00204 AC XY: 152 AN XY: 74510

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0114

Gnomad4 NFE AF: 0.000970

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000817 Hom.: 1

Bravo AF: 0.000805

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

NADSYN1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	1.8
Dann	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs142412970; hg19: chr11-71175174;