Menu
GeneBe

7-106261678-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.037 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 472 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NAMPTNM_005746.3 linkuse as main transcriptc.999T>C p.Pro333= synonymous_variant 8/11 ENST00000222553.8
NAMPTXM_047419699.1 linkuse as main transcriptc.999T>C p.Pro333= synonymous_variant 9/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NAMPTENST00000222553.8 linkuse as main transcriptc.999T>C p.Pro333= synonymous_variant 8/111 NM_005746.3 P4

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00310
AC:
472
AN:
152188
Hom.:
2
Cov.:
32
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.:
3
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.:
11
Cov.:
30
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00310
AC:
472
AN:
152306
Hom.:
2
Cov.:
32
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.:
0
Bravo
AF:
0.00254
EpiCase
AF:
0.00409
EpiControl
AF:
0.00445

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

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.

Other links and lift over

dbSNP: rs137878255; hg19: chr7-105902124; COSMIC: COSV99748471; COSMIC: COSV99748471; API