Variant 11-71458501-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018161.5(NADSYN1):c.220G>C(p.Val74Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 1,612,740 control chromosomes in the GnomAD database, including 400,882 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.58 ( 27972 hom., cov: 32)

Exomes 𝑓: 0.69 ( 372910 hom. )

Consequence

NADSYN1
NM_018161.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.230

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.6351913E-6).

BP6

Variant 11-71458501-G-C is Benign according to our data. Variant chr11-71458501-G-C is described in ClinVar as [Benign]. Clinvar id is 1248202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NADSYN1	NM_018161.5 link	c.220G>C	p.Val74Leu	missense_variant	Exon 3 of 21	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.220G>C	p.Val74Leu	missense_variant	Exon 3 of 21	1	NM_018161.5	ENSP00000326424.2		Q6IA69-1

Frequencies

GnomAD3 genomes

AF:

0.582

AC:

88408

AN:

151872

Hom.:

27948

Cov.:

show subpopulations

Gnomad AFR

AF:

0.409

Gnomad AMI

AF:

0.687

Gnomad AMR

AF:

0.502

Gnomad ASJ

AF:

0.614

Gnomad EAS

AF:

0.383

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.588

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.744

Gnomad OTH

AF:

0.560

GnomAD3 exomes

AF:

0.566

AC:

142274

AN:

251232

Hom.:

44671

AF XY:

0.561

AC XY:

76120

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.404

Gnomad AMR exome

AF:

0.486

Gnomad ASJ exome

AF:

0.621

Gnomad EAS exome

AF:

0.390

Gnomad SAS exome

AF:

0.213

Gnomad FIN exome

AF:

0.600

Gnomad NFE exome

AF:

0.724

Gnomad OTH exome

AF:

0.603

GnomAD4 exome

AF:

0.694

AC:

1014432

AN:

1460750

Hom.:

372910

Cov.:

AF XY:

0.681

AC XY:

494624

AN XY:

726810

show subpopulations

Gnomad4 AFR exome

AF:

0.384

Gnomad4 AMR exome

AF:

0.487

Gnomad4 ASJ exome

AF:

0.622

Gnomad4 EAS exome

AF:

0.347

Gnomad4 SAS exome

AF:

0.220

Gnomad4 FIN exome

AF:

0.606

Gnomad4 NFE exome

AF:

0.771

Gnomad4 OTH exome

AF:

0.640

GnomAD4 genome

AF:

0.582

AC:

88479

AN:

151990

Hom.:

27972

Cov.:

AF XY:

0.565

AC XY:

41959

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.410

Gnomad4 AMR

AF:

0.502

Gnomad4 ASJ

AF:

0.614

Gnomad4 EAS

AF:

0.384

Gnomad4 SAS

AF:

0.212

Gnomad4 FIN

AF:

0.588

Gnomad4 NFE

AF:

0.744

Gnomad4 OTH

AF:

0.554

Alfa

AF:

0.700

Hom.:

26871

Bravo

AF:

0.579

TwinsUK

AF:

0.774

AC:

2869

ALSPAC

AF:

0.763

AC:

2942

ESP6500AA

AF:

0.426

AC:

1874

ESP6500EA

AF:

0.744

AC:

6393

ExAC

AF:

0.560

AC:

67942

Asia WGS

AF:

0.287

AC:

1001

AN:

3478

EpiCase

AF:

0.749

EpiControl

AF:

0.743

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 23, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Vertebral, cardiac, renal, and limb defects syndrome 3

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.20

CADD

Benign

0.10

DANN

Benign

0.37

DEOGEN2

Benign

0.029

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0000026

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-2.4

PrimateAI

Uncertain

0.56

PROVEAN

Benign

2.6

REVEL

Uncertain

0.47

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.071

MutPred

0.24

Gain of helix (P = 0.062);

MPC

0.17

ClinPred

0.0039

GERP RS

-2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.041

gMVP

0.64

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