NM_018161.5:c.147-1439A>G

Variant summary

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

The NM_018161.5(NADSYN1):​c.147-1439A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 152,134 control chromosomes in the GnomAD database, including 29,921 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 0.61 ( 29921 hom., cov: 34)

Consequence

NADSYN1
NM_018161.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.398

Publications

23 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

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=-0.93).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NADSYN1NM_018161.5 linkc.147-1439A>G intron_variant Intron 2 of 20 ENST00000319023.7 NP_060631.2 Q6IA69-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NADSYN1ENST00000319023.7 linkc.147-1439A>G intron_variant Intron 2 of 20 1 NM_018161.5 ENSP00000326424.2 Q6IA69-1

Frequencies

GnomAD3 genomes
AF:
0.610
AC:
92673
AN:
152014
Hom.:
29878
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.505
Gnomad AMI
AF:
0.689
Gnomad AMR
AF:
0.512
Gnomad ASJ
AF:
0.615
Gnomad EAS
AF:
0.381
Gnomad SAS
AF:
0.210
Gnomad FIN
AF:
0.589
Gnomad MID
AF:
0.459
Gnomad NFE
AF:
0.744
Gnomad OTH
AF:
0.577
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.610
AC:
92764
AN:
152134
Hom.:
29921
Cov.:
34
AF XY:
0.592
AC XY:
44046
AN XY:
74390
show subpopulations
African (AFR)
AF:
0.506
AC:
21006
AN:
41500
American (AMR)
AF:
0.512
AC:
7828
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
0.615
AC:
2134
AN:
3472
East Asian (EAS)
AF:
0.381
AC:
1960
AN:
5138
South Asian (SAS)
AF:
0.212
AC:
1023
AN:
4828
European-Finnish (FIN)
AF:
0.589
AC:
6237
AN:
10596
Middle Eastern (MID)
AF:
0.476
AC:
139
AN:
292
European-Non Finnish (NFE)
AF:
0.744
AC:
50606
AN:
67992
Other (OTH)
AF:
0.571
AC:
1204
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
1737
3473
5210
6946
8683
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
740
1480
2220
2960
3700
<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:
0.621
Hom.:
5134
Bravo
AF:
0.609

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
0.52
DANN
Benign
0.30
PhyloP100
-0.40
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

Publications

Other links and lift over

dbSNP: rs4944957; hg19: chr11-71168035; API