chr7-106263458-T-C

Variant names:

• chr7-106263458-T-C
• rs2302559
• NM_005746.3:c.903A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005746.3(NAMPT):​c.903A>G​(p.Ser301Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 1,559,824 control chromosomes in the GnomAD database, including 335,624 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.65 (32259 hom., cov: 31)
  • Exomes 𝑓: 0.65 (303365 hom.)
• Consequence: NAMPT NM_005746.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• Publications: 33 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=-0.12 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005746.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAMPT	NM_005746.3	MANE Select	c.903A>G	p.Ser301Ser	synonymous	Exon 7 of 11	NP_005737.1	P43490

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAMPT	ENST00000222553.8	TSL:1 MANE Select	c.903A>G	p.Ser301Ser	synonymous	Exon 7 of 11	ENSP00000222553.3	P43490
	NAMPT	ENST00000354289.9	TSL:1	c.903A>G	p.Ser301Ser	synonymous	Exon 7 of 8	ENSP00000346242.4	A0A0C4DFS8
	NAMPT	ENST00000968694.1		c.903A>G	p.Ser301Ser	synonymous	Exon 7 of 12	ENSP00000638753.1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98263 AN: 151704 Hom.: 32222 Cov.: 31

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.663

GnomAD2 exomes AF: 0.695 AC: 168681 AN: 242776 AF XY: 0.690

Gnomad AFR exome AF: 0.583

Gnomad AMR exome AF: 0.820

Gnomad ASJ exome AF: 0.643

Gnomad EAS exome AF: 0.917

Gnomad FIN exome AF: 0.728

Gnomad NFE exome AF: 0.636

Gnomad OTH exome AF: 0.689

GnomAD4 exome AF: 0.649 AC: 913910 AN: 1408002 Hom.: 303365 Cov.: 34 AF XY: 0.650 AC XY: 455949 AN XY: 700954

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.576 AC: 18481 AN: 32110

American (AMR) AF: 0.817 AC: 35312 AN: 43230

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 15551 AN: 24756

East Asian (EAS) AF: 0.908 AC: 35810 AN: 39430

South Asian (SAS) AF: 0.686 AC: 56940 AN: 83058

European-Finnish (FIN) AF: 0.723 AC: 38022 AN: 52616

Middle Eastern (MID) AF: 0.698 AC: 3898 AN: 5582

European-Non Finnish (NFE) AF: 0.628 AC: 671124 AN: 1068902

Other (OTH) AF: 0.665 AC: 38772 AN: 58318

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.648 AC: 98366 AN: 151822 Hom.: 32259 Cov.: 31 AF XY: 0.659 AC XY: 48920 AN XY: 74238

African (AFR) AF: 0.579 AC: 23990 AN: 41410

American (AMR) AF: 0.743 AC: 11340 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2185 AN: 3466

East Asian (EAS) AF: 0.911 AC: 4714 AN: 5176

South Asian (SAS) AF: 0.689 AC: 3319 AN: 4816

European-Finnish (FIN) AF: 0.740 AC: 7825 AN: 10580

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42842 AN: 67792

Other (OTH) AF: 0.666 AC: 1404 AN: 2108

Alfa AF: 0.572 Hom.: 3193

Bravo AF: 0.650

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	3.8
DANN	Benign	0.57
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2302559; hg19: chr7-105903904; COSMIC: COSV108072338; COSMIC: COSV108072338;