Genetic Variant NM_145201.6:c.1023-38G>T (chr8-143576200-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145201.6(NAPRT):c.1023-38G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,046 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. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

NAPRT
NM_145201.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.58

Publications

0 publications found

Variant links:

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]

NAPRT links:

ENSG00000255050 (HGNC:):

ENSG00000255050 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145201.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NAPRT	NM_145201.6	MANE Select	c.1023-38G>T	intron	N/A	NP_660202.3
NAPRT	NM_001286829.2		c.1023-38G>T	intron	N/A	NP_001273758.1
NAPRT	NM_001363145.1		c.1023-38G>T	intron	N/A	NP_001350074.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NAPRT	ENST00000449291.7	TSL:1 MANE Select	c.1023-38G>T	intron	N/A	ENSP00000401508.2
NAPRT	ENST00000426292.7	TSL:1	c.1023-38G>T	intron	N/A	ENSP00000390949.3
NAPRT	ENST00000340490.7	TSL:1	n.1023-38G>T	intron	N/A	ENSP00000341136.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.23e-7

AC:

AN:

1383046

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

680984

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

31478

American (AMR)

AF:

0.00

AC:

AN:

35408

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22420

East Asian (EAS)

AF:

0.00

AC:

AN:

38292

South Asian (SAS)

AF:

0.00

AC:

AN:

77380

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49472

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5482

European-Non Finnish (NFE)

AF:

9.38e-7

AC:

AN:

1066154

Other (OTH)

AF:

0.00

AC:

AN:

56960

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.4

(source)

DANN

Benign

0.57

PhyloP100

-1.6

BranchPoint Hunter

0.0

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over