NM_005746.3:c.970-92G>A

Variant names:

• chr7-106261799-C-T
• rs41496055
• NM_005746.3:c.970-92G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_005746.3(NAMPT):​c.970-92G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000663 in 1,356,710 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: NAMPT NM_005746.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.346
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAMPT	NM_005746.3	c.970-92G>A		intron_variant	Intron 7 of 10	ENST00000222553.8	NP_005737.1
NAMPT	XM_047419699.1	c.970-92G>A		intron_variant	Intron 8 of 11		XP_047275655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAMPT	ENST00000222553.8	c.970-92G>A		intron_variant	Intron 7 of 10	1	NM_005746.3	ENSP00000222553.3

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151884 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000498 AC: 6 AN: 1204826 Hom.: 0 AF XY: 0.00000494 AC XY: 3 AN XY: 607894

African (AFR) AF: 0.0000753 AC: 2 AN: 26554

American (AMR) AF: 0.00 AC: 0 AN: 33208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22146

East Asian (EAS) AF: 0.00 AC: 0 AN: 37850

South Asian (SAS) AF: 0.0000136 AC: 1 AN: 73280

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50064

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5114

European-Non Finnish (NFE) AF: 0.00000221 AC: 2 AN: 905660

Other (OTH) AF: 0.0000196 AC: 1 AN: 50950

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151884 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74168

African (AFR) AF: 0.0000725 AC: 3 AN: 41400

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67902

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.66
PhyloP100		0.35

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: rs41496055; hg19: chr7-105902245;