Variant 13-113429005-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001394807.1(ADPRHL1):c.593G>A(p.Arg198Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000067 in 1,612,740 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000064 ( 1 hom. )

Consequence

ADPRHL1
NM_001394807.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

Variant links:

Genes affected

ADPRHL1 (HGNC:21303): (ADP-ribosylhydrolase like 1) ADP-ribosylation is a reversible posttranslational modification used to regulate protein function. ADP-ribosyltransferases (see ART1; MIM 601625) transfer ADP-ribose from NAD+ to the target protein, and ADP-ribosylhydrolases, such as ADPRHL1, reverse the reaction (Glowacki et al., 2002 [PubMed 12070318]).[supplied by OMIM, Mar 2008]

ADPRHL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.046586633).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADPRHL1	NM_001394807.1 linkuse as main transcript	c.593G>A	p.Arg198Gln	missense_variant	4/8	ENST00000612156.3	NP_001381736.1
ADPRHL1	NM_138430.5 linkuse as main transcript	c.593G>A	p.Arg198Gln	missense_variant	4/7		NP_612439.2
ADPRHL1	NM_199162.3 linkuse as main transcript	c.347G>A	p.Arg116Gln	missense_variant	4/7		NP_954631.1
ADPRHL1	XM_047430086.1 linkuse as main transcript	c.347G>A	p.Arg116Gln	missense_variant	4/8		XP_047286042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADPRHL1	ENST00000612156.3 linkuse as main transcript	c.593G>A	p.Arg198Gln	missense_variant	4/8	5	NM_001394807.1	ENSP00000489048
ADPRHL1	ENST00000375418.8 linkuse as main transcript	c.593G>A	p.Arg198Gln	missense_variant	4/7	1		ENSP00000364567	P1	Q8NDY3-1
ADPRHL1	ENST00000356501.8 linkuse as main transcript	c.347G>A	p.Arg116Gln	missense_variant	4/7	1		ENSP00000348894		Q8NDY3-2
ADPRHL1	ENST00000413169.2 linkuse as main transcript	c.347G>A	p.Arg116Gln	missense_variant	4/5	3		ENSP00000416213

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000923

AC:

AN:

249264

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135320

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.000744

Gnomad NFE exome

AF:

0.0000268

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000644

AC:

AN:

1460530

Hom.:

Cov.:

AF XY:

0.0000743

AC XY:

AN XY:

726530

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.000595

Gnomad4 NFE exome

AF:

0.0000423

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000783

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000660

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.593G>A (p.R198Q) alteration is located in exon 4 (coding exon 4) of the ADPRHL1 gene. This alteration results from a G to A substitution at nucleotide position 593, causing the arginine (R) at amino acid position 198 to be replaced by a glutamine (Q). 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

0.067

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.016

T;.;T;.

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.85

T;T;D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.047

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

.;.;L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

0.030

.;N;N;N

REVEL

Benign

0.083

Sift

Benign

0.23

.;T;T;T

Sift4G

Uncertain

0.028

D;T;T;T

Polyphen

0.60

.;.;P;.

Vest4

0.17

MVP

0.34

MPC

0.11

ClinPred

0.059

GERP RS

-2.2

Varity_R

0.033

gMVP

0.24

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over