rs142412970

Variant names:

• chr11-71464128-G-A
• rs142412970
• NM_018161.5:c.393G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-71464128-G-A
• chr11-71464128-G-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_018161.5(NADSYN1):​c.393G>A​(p.Pro131Pro) 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
• Publications: 3 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 -11 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 VariationId is 3025011.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.65 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

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.393G>A	p.Pro131Pro	synonymous	Exon 5 of 21	NP_060631.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NADSYN1	ENST00000319023.7	TSL:1 MANE Select	c.393G>A	p.Pro131Pro	synonymous	Exon 5 of 21	ENSP00000326424.2	Q6IA69-1
	NADSYN1	ENST00000528509.5	TSL:1	n.393G>A		non_coding_transcript_exon	Exon 5 of 10	ENSP00000433472.1	E9PKY6
	NADSYN1	ENST00000859578.1		c.393G>A	p.Pro131Pro	synonymous	Exon 5 of 22	ENSP00000529637.1

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

GnomAD2 exomes AF: 0.00174 AC: 422 AN: 242214 AF XY: 0.00176

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 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

African (AFR) AF: 0.0000598 AC: 2 AN: 33442

American (AMR) AF: 0.00113 AC: 50 AN: 44298

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26050

East Asian (EAS) AF: 0.00134 AC: 53 AN: 39612

South Asian (SAS) AF: 0.000376 AC: 32 AN: 85218

European-Finnish (FIN) AF: 0.0105 AC: 556 AN: 52722

Middle Eastern (MID) AF: 0.000868 AC: 5 AN: 5762

European-Non Finnish (NFE) AF: 0.000703 AC: 781 AN: 1110350

Other (OTH) AF: 0.000996 AC: 60 AN: 60256

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

African (AFR) AF: 0.000144 AC: 6 AN: 41594

American (AMR) AF: 0.00118 AC: 18 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4832

European-Finnish (FIN) AF: 0.0114 AC: 121 AN: 10626

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000970 AC: 66 AN: 68034

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000810 Hom.: 1

Bravo AF: 0.000805

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.8
DANN	Benign	0.63
PhyloP100		-4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs142412970; hg19: chr11-71175174;