Variant 7-106251135-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2

The NM_005746.3(NAMPT):c.1424A>C(p.Glu475Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000128 in 1,607,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000080 ( 0 hom. )

Consequence

NAMPT
NM_005746.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.84

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 -7 ACMG points.

PP2

Missense variant where missense usually causes diseases, NAMPT

BP4

Computational evidence support a benign effect (MetaRNN=0.03897196).

BS2

High AC in GnomAd at 89 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAMPT	NM_005746.3 linkuse as main transcript	c.1424A>C	p.Glu475Ala	missense_variant	11/11	ENST00000222553.8
NAMPT	XM_047419699.1 linkuse as main transcript	c.1424A>C	p.Glu475Ala	missense_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAMPT	ENST00000222553.8 linkuse as main transcript	c.1424A>C	p.Glu475Ala	missense_variant	11/11	1	NM_005746.3	P4

Frequencies

GnomAD3 genomes

AF:

0.000585

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000144

AC:

AN:

250848

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135582

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000804

AC:

117

AN:

1454776

Hom.:

Cov.:

AF XY:

0.0000690

AC XY:

AN XY:

724246

show subpopulations

Gnomad4 AFR exome

AF:

0.00222

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.0000768

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000172

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000585

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00202

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000313

Hom.:

Bravo

AF:

0.000601

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.1424A>C (p.E475A) alteration is located in exon 11 (coding exon 11) of the NAMPT gene. This alteration results from a A to C substitution at nucleotide position 1424, causing the glutamic acid (E) at amino acid position 475 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.040

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.44

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.0046

MetaRNN

Benign

0.039

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.19

Sift

Benign

0.13

Sift4G

Benign

0.16

Polyphen

0.096

Vest4

0.62

MVP

0.33

MPC

1.3

ClinPred

0.099

GERP RS

5.8

Varity_R

0.68

gMVP

0.85

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