rs2015562

Variant names:

• chr8-143578087-G-A
• rs2015562
• NM_145201.6:c.226+6C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-143578087-G-A
• chr8-143578087-G-C
• chr8-143578087-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145201.6(NAPRT):​c.226+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NAPRT NM_145201.6 splice_region, intron
• Scores: Splicing: ADA: 0.00006132
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.925
• Publications: 18 publications found

Genes affected

NAPRT (HGNC:30450): (nicotinate phosphoribosyltransferase) Nicotinic acid (NA; niacin) is converted by nicotinic acid phosphoribosyltransferase (NAPRT; EC 2.4.2.11) to NA mononucleotide (NaMN), which is then converted to NA adenine dinucleotide (NaAD), and finally to nicotinamide adenine dinucleotide (NAD), which serves as a coenzyme in cellular redox reactions and is an essential component of a variety of processes in cellular metabolism including response to stress (Hara et al., 2007).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAPRT	NM_145201.6	c.226+6C>T		splice_region_variant, intron_variant	Intron 1 of 12	ENST00000449291.7	NP_660202.3
NAPRT	NM_001286829.2	c.226+6C>T		splice_region_variant, intron_variant	Intron 1 of 12		NP_001273758.1
NAPRT	NM_001363145.1	c.226+6C>T		splice_region_variant, intron_variant	Intron 1 of 11		NP_001350074.1
NAPRT	NM_001363146.1	c.-343+6C>T		splice_region_variant, intron_variant	Intron 1 of 11		NP_001350075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAPRT	ENST00000449291.7	c.226+6C>T		splice_region_variant, intron_variant	Intron 1 of 12	1	NM_145201.6	ENSP00000401508.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1366400 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 673848

African (AFR) AF: 0.00 AC: 0 AN: 29818

American (AMR) AF: 0.00 AC: 0 AN: 31112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22024

East Asian (EAS) AF: 0.00 AC: 0 AN: 36334

South Asian (SAS) AF: 0.00 AC: 0 AN: 76578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4390

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1072274

Other (OTH) AF: 0.00 AC: 0 AN: 56418

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 923

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.89
PhyloP100		0.93
PromoterAI		0.054	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000061
dbscSNV1_RF	Benign	0.0040
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: rs2015562; hg19: chr8-144660257;