dbSNP rs12800438: NADSYN1:c.263+1413G>A (chr11-71459957-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018161.5(NADSYN1):c.263+1413G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 152,282 control chromosomes in the GnomAD database, including 27,626 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 0.58 ( 27592 hom., cov: 34)

Exomes 𝑓: 0.68 ( 34 hom. )

Consequence

NADSYN1
NM_018161.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.46

Publications

43 publications found

Variant links:

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

NADSYN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.738 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.263+1413G>A		intron	N/A	NP_060631.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NADSYN1	ENST00000319023.7	TSL:1 MANE Select	c.263+1413G>A	intron	N/A	ENSP00000326424.2	Q6IA69-1
NADSYN1	ENST00000528509.5	TSL:1	n.263+1413G>A	intron	N/A	ENSP00000433472.1	E9PKY6
NADSYN1	ENST00000859578.1		c.263+1413G>A	intron	N/A	ENSP00000529637.1

Frequencies

GnomAD3 genomes

AF:

0.575

AC:

87468

AN:

152036

Hom.:

27563

Cov.:

show subpopulations

Gnomad AFR

AF:

0.386

Gnomad AMI

AF:

0.689

Gnomad AMR

AF:

0.499

Gnomad ASJ

AF:

0.615

Gnomad EAS

AF:

0.382

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.590

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.744

Gnomad OTH

AF:

0.556

GnomAD4 exome

AF:

0.680

AC:

AN:

128

Hom.:

Cov.:

AF XY:

0.680

AC XY:

AN XY:

100

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.750

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.549

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.575

AC:

87544

AN:

152154

Hom.:

27592

Cov.:

AF XY:

0.559

AC XY:

41573

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.387

AC:

16048

AN:

41496

American (AMR)

AF:

0.499

AC:

7630

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.615

AC:

2134

AN:

3472

East Asian (EAS)

AF:

0.383

AC:

1980

AN:

5170

South Asian (SAS)

AF:

0.211

AC:

1019

AN:

4828

European-Finnish (FIN)

AF:

0.590

AC:

6239

AN:

10582

Middle Eastern (MID)

AF:

0.469

AC:

138

AN:

294

European-Non Finnish (NFE)

AF:

0.744

AC:

50565

AN:

68004

Other (OTH)

AF:

0.550

AC:

1164

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1722

3443

5165

6886

8608

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

710

1420

2130

2840

3550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.681

Hom.:

108073

Bravo

AF:

0.571

Asia WGS

AF:

0.286

AC:

997

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.73

(source)

DANN

Benign

0.61

PhyloP100

-2.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over