dbSNP rs3794060: NADSYN1:n.*1442C>T (chr11-71476633-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000528509.5(NADSYN1):n.*1442C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 984,538 control chromosomes in the GnomAD database, including 269,239 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 0.53 ( 25285 hom., cov: 32)

Exomes 𝑓: 0.75 ( 243954 hom. )

Consequence

NADSYN1
ENST00000528509.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.43

Publications

63 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
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=-1.01).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NADSYN1	NM_018161.5 link	c.799-1762C>T		intron_variant	Intron 9 of 20	ENST00000319023.7	NP_060631.2	Q6IA69-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NADSYN1	ENST00000319023.7 link	c.799-1762C>T		intron_variant	Intron 9 of 20	1	NM_018161.5	ENSP00000326424.2		Q6IA69-1

Frequencies

GnomAD3 genomes

AF:

0.528

AC:

80194

AN:

151800

Hom.:

25281

Cov.:

show subpopulations

Gnomad AFR

AF:

0.222

Gnomad AMI

AF:

0.723

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.615

Gnomad EAS

AF:

0.381

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.588

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.743

Gnomad OTH

AF:

0.519

GnomAD4 exome

AF:

0.755

AC:

628591

AN:

832620

Hom.:

243954

Cov.:

AF XY:

0.755

AC XY:

290265

AN XY:

384606

show subpopulations

African (AFR)

AF:

0.167

AC:

2642

AN:

15774

American (AMR)

AF:

0.491

AC:

523

AN:

1066

Ashkenazi Jewish (ASJ)

AF:

0.615

AC:

3166

AN:

5144

East Asian (EAS)

AF:

0.358

AC:

1304

AN:

3646

South Asian (SAS)

AF:

0.218

AC:

3598

AN:

16518

European-Finnish (FIN)

AF:

0.586

AC:

177

AN:

302

Middle Eastern (MID)

AF:

0.502

AC:

812

AN:

1618

European-Non Finnish (NFE)

AF:

0.786

AC:

598223

AN:

761272

Other (OTH)

AF:

0.665

AC:

18146

AN:

27280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

Heterozygous variant carriers

7266

14533

21799

29066

36332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19014

38028

57042

76056

95070

<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:

0.528

AC:

80207

AN:

151918

Hom.:

25285

Cov.:

AF XY:

0.513

AC XY:

38040

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.221

AC:

9161

AN:

41424

American (AMR)

AF:

0.484

AC:

7389

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.615

AC:

2135

AN:

3472

East Asian (EAS)

AF:

0.382

AC:

1965

AN:

5146

South Asian (SAS)

AF:

0.210

AC:

1014

AN:

4818

European-Finnish (FIN)

AF:

0.588

AC:

6185

AN:

10520

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.743

AC:

50484

AN:

67964

Other (OTH)

AF:

0.513

AC:

1079

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1542

3083

4625

6166

7708

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

656

1312

1968

2624

3280

<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:

0.653

Hom.:

41551

Bravo

AF:

0.517

Asia WGS

AF:

0.271

AC:

945

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.52

(source)

DANN

Benign

0.48

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over