Variant 7-106261678-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005746.3(NAMPT):c.999T>C(p.Pro333=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00296 in 1,603,790 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 11 hom. )

Consequence

NAMPT
NM_005746.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0370

Variant links:

Genes affected

NAMPT (HGNC:30092): (nicotinamide phosphoribosyltransferase) This gene encodes a protein that catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, one step in the biosynthesis of nicotinamide adenine dinucleotide. The protein belongs to the nicotinic acid phosphoribosyltransferase (NAPRTase) family and is thought to be involved in many important biological processes, including metabolism, stress response and aging. This gene has a pseudogene on chromosome 10. [provided by RefSeq, Feb 2011]

NAMPT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 7-106261678-A-G is Benign according to our data. Variant chr7-106261678-A-G is described in ClinVar as [Benign]. Clinvar id is 774661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.037 with no splicing effect.

BS2

High AC in GnomAd4 at 472 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAMPT	NM_005746.3 linkuse as main transcript	c.999T>C	p.Pro333=	synonymous_variant	8/11	ENST00000222553.8	NP_005737.1
NAMPT	XM_047419699.1 linkuse as main transcript	c.999T>C	p.Pro333=	synonymous_variant	9/12		XP_047275655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAMPT	ENST00000222553.8 linkuse as main transcript	c.999T>C	p.Pro333=	synonymous_variant	8/11	1	NM_005746.3	ENSP00000222553	P4

Frequencies

GnomAD3 genomes

AF:

0.00310

AC:

472

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00791

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00376

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00307

AC:

772

AN:

251062

Hom.:

AF XY:

0.00311

AC XY:

422

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.000740

Gnomad AMR exome

AF:

0.00374

Gnomad ASJ exome

AF:

0.00517

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000981

Gnomad FIN exome

AF:

0.00605

Gnomad NFE exome

AF:

0.00338

Gnomad OTH exome

AF:

0.00556

GnomAD4 exome

AF:

0.00295

AC:

4281

AN:

1451484

Hom.:

Cov.:

AF XY:

0.00294

AC XY:

2122

AN XY:

722830

show subpopulations

Gnomad4 AFR exome

AF:

0.000422

Gnomad4 AMR exome

AF:

0.00423

Gnomad4 ASJ exome

AF:

0.00518

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00131

Gnomad4 FIN exome

AF:

0.00594

Gnomad4 NFE exome

AF:

0.00301

Gnomad4 OTH exome

AF:

0.00295

GnomAD4 genome

AF:

0.00310

AC:

472

AN:

152306

Hom.:

Cov.:

AF XY:

0.00314

AC XY:

234

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.00516

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00791

Gnomad4 NFE

AF:

0.00377

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00338

Hom.:

Bravo

AF:

0.00254

EpiCase

AF:

0.00409

EpiControl

AF:

0.00445

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.2

DANN

Benign

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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