Variant 11-71463406-A-G 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.264-26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 1,604,516 control chromosomes in the GnomAD database, including 397,031 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.57 ( 27351 hom., cov: 31)

Exomes 𝑓: 0.69 ( 369680 hom. )

Consequence

NADSYN1
NM_018161.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.48

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 11-71463406-A-G is Benign according to our data. Variant chr11-71463406-A-G is described in ClinVar as [Benign]. Clinvar id is 1321836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NADSYN1	NM_018161.5 link	c.264-26A>G		intron_variant	Intron 3 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.264-26A>G		intron_variant	Intron 3 of 20	1	NM_018161.5	ENSP00000326424.2		Q6IA69-1

Frequencies

GnomAD3 genomes

AF:

0.572

AC:

86830

AN:

151830

Hom.:

27323

Cov.:

show subpopulations

Gnomad AFR

AF:

0.373

Gnomad AMI

AF:

0.687

Gnomad AMR

AF:

0.499

Gnomad ASJ

AF:

0.615

Gnomad EAS

AF:

0.382

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.588

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.744

Gnomad OTH

AF:

0.553

GnomAD3 exomes

AF:

0.563

AC:

140738

AN:

249914

Hom.:

44076

AF XY:

0.558

AC XY:

75409

AN XY:

135116

show subpopulations

Gnomad AFR exome

AF:

0.368

Gnomad AMR exome

AF:

0.484

Gnomad ASJ exome

AF:

0.621

Gnomad EAS exome

AF:

0.387

Gnomad SAS exome

AF:

0.213

Gnomad FIN exome

AF:

0.600

Gnomad NFE exome

AF:

0.724

Gnomad OTH exome

AF:

0.602

GnomAD4 exome

AF:

0.693

AC:

1006308

AN:

1452568

Hom.:

369680

Cov.:

AF XY:

0.679

AC XY:

491068

AN XY:

723176

show subpopulations

Gnomad4 AFR exome

AF:

0.346

Gnomad4 AMR exome

AF:

0.485

Gnomad4 ASJ exome

AF:

0.622

Gnomad4 EAS exome

AF:

0.346

Gnomad4 SAS exome

AF:

0.220

Gnomad4 FIN exome

AF:

0.607

Gnomad4 NFE exome

AF:

0.771

Gnomad4 OTH exome

AF:

0.637

GnomAD4 genome

AF:

0.572

AC:

86906

AN:

151948

Hom.:

27351

Cov.:

AF XY:

0.556

AC XY:

41268

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.374

Gnomad4 AMR

AF:

0.498

Gnomad4 ASJ

AF:

0.615

Gnomad4 EAS

AF:

0.382

Gnomad4 SAS

AF:

0.211

Gnomad4 FIN

AF:

0.588

Gnomad4 NFE

AF:

0.744

Gnomad4 OTH

AF:

0.546

Alfa

AF:

0.695

Hom.:

37760

Bravo

AF:

0.567

Asia WGS

AF:

0.285

AC:

995

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0070

DANN

Benign

0.27

BranchPoint Hunter

0.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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