Variant 11-71473632-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018161.5(NADSYN1):c.612A>C(p.Gln204His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,613,280 control chromosomes in the GnomAD database, including 806,625 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 1.0 ( 76165 hom., cov: 35)

Exomes 𝑓: 1.0 ( 730460 hom. )

Consequence

NADSYN1
NM_018161.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.186

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.2554227E-7).

BP6

Variant 11-71473632-A-C is Benign according to our data. Variant chr11-71473632-A-C is described in ClinVar as [Benign]. Clinvar id is 1321840.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NADSYN1	NM_018161.5 linkuse as main transcript	c.612A>C	p.Gln204His	missense_variant	8/21	ENST00000319023.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NADSYN1	ENST00000319023.7 linkuse as main transcript	c.612A>C	p.Gln204His	missense_variant	8/21	1	NM_018161.5	P1	Q6IA69-1
NADSYN1	ENST00000528509.5 linkuse as main transcript	c.612A>C	p.Gln204His	missense_variant, NMD_transcript_variant	8/10	1
NADSYN1	ENST00000525200.5 linkuse as main transcript	c.513A>C	p.Gln171His	missense_variant, NMD_transcript_variant	7/21	2
NADSYN1	ENST00000530534.1 linkuse as main transcript			upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

1.00

AC:

152215

AN:

152218

Hom.:

76106

Cov.:

show subpopulations

Gnomad AFR

AF:

1.00

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

1.00

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

1.00

GnomAD3 exomes

AF:

1.00

AC:

250495

AN:

250498

Hom.:

125246

AF XY:

1.00

AC XY:

135736

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

1.00

Gnomad AMR exome

AF:

1.00

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

AF:

1.00

AC:

1460932

AN:

1460944

Hom.:

730460

Cov.:

AF XY:

1.00

AC XY:

726760

AN XY:

726768

show subpopulations

Gnomad4 AFR exome

AF:

1.00

Gnomad4 AMR exome

AF:

1.00

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

1.00

GnomAD4 genome

AF:

1.00

AC:

152333

AN:

152336

Hom.:

76165

Cov.:

AF XY:

1.00

AC XY:

74493

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

1.00

Gnomad4 AMR

AF:

1.00

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

1.00

Alfa

AF:

1.00

Hom.:

82147

Bravo

AF:

1.00

TwinsUK

AF:

1.00

AC:

3708

ALSPAC

AF:

1.00

AC:

3854

ExAC

AF:

1.00

AC:

121371

Asia WGS

AF:

1.00

AC:

3478

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Vertebral, cardiac, renal, and limb defects syndrome 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.033

BayesDel_addAF

Benign

-0.033

BayesDel_noAF

Benign

-0.29

Cadd

Benign

0.98

Dann

Benign

0.15

DEOGEN2

Benign

0.033

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.65

MetaRNN

Benign

6.3e-7

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-3.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.55

PROVEAN

Benign

5.2

REVEL

Uncertain

0.35

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.072

MutPred

0.26

Gain of catalytic residue at L206 (P = 0.0679);

MPC

0.16

ClinPred

0.0020

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.071

gMVP

0.68

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over