7-106263496-T-C

Variant names:

• chr7-106263496-T-C
• NM_005746.3:c.865A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005746.3(NAMPT):​c.865A>G​(p.Lys289Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAMPT NM_005746.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.87

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19657555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAMPT	NM_005746.3	c.865A>G	p.Lys289Glu	missense_variant	Exon 7 of 11	ENST00000222553.8	NP_005737.1
NAMPT	XM_047419699.1	c.865A>G	p.Lys289Glu	missense_variant	Exon 8 of 12		XP_047275655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAMPT	ENST00000222553.8	c.865A>G	p.Lys289Glu	missense_variant	Exon 7 of 11	1	NM_005746.3	ENSP00000222553.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 23, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.865A>G (p.K289E) alteration is located in exon 7 (coding exon 7) of the NAMPT gene. This alteration results from a A to G substitution at nucleotide position 865, causing the lysine (K) at amino acid position 289 to be replaced by a glutamic acid (E). 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	0.17
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.057
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.32	N;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.68	N;N
REVEL	Benign	0.20
Sift	Benign	0.78	T;T
Sift4G	Benign	0.77	T;T
Polyphen		0.87	P;.
Vest4		0.58
MutPred		0.47		Loss of ubiquitination at K289 (P = 0.0192);Loss of ubiquitination at K289 (P = 0.0192);
MVP		0.58
MPC		1.6
ClinPred		0.64	D
GERP RS		5.4
Varity_R		0.61
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-105903942;