Variant 13-113425059-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.767G>A(p.Arg256Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00012 in 1,613,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

ADPRHL1
NM_001394807.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.62

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=0.011157215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADPRHL1	NM_001394807.1 linkuse as main transcript	c.767G>A	p.Arg256Lys	missense_variant	5/8	ENST00000612156.3	NP_001381736.1
ADPRHL1	NM_138430.5 linkuse as main transcript	c.767G>A	p.Arg256Lys	missense_variant	5/7		NP_612439.2	Q8NDY3-1
ADPRHL1	NM_199162.3 linkuse as main transcript	c.521G>A	p.Arg174Lys	missense_variant	5/7		NP_954631.1	Q8NDY3-2
ADPRHL1	XM_047430086.1 linkuse as main transcript	c.521G>A	p.Arg174Lys	missense_variant	5/8		XP_047286042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADPRHL1	ENST00000612156.3 linkuse as main transcript	c.767G>A	p.Arg256Lys	missense_variant	5/8	5	NM_001394807.1	ENSP00000489048.1	A0A0U1RQK4
ADPRHL1	ENST00000375418.8 linkuse as main transcript	c.767G>A	p.Arg256Lys	missense_variant	5/7	1		ENSP00000364567.3	Q8NDY3-1
ADPRHL1	ENST00000356501.8 linkuse as main transcript	c.521G>A	p.Arg174Lys	missense_variant	5/7	1		ENSP00000348894.4	Q8NDY3-2
ADPRHL1	ENST00000413169.2 linkuse as main transcript	c.521G>A	p.Arg174Lys	missense_variant	5/5	3		ENSP00000416213.1	X6RL45

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00606

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000243

AC:

AN:

250644

Hom.:

AF XY:

0.000199

AC XY:

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00527

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000115

AC:

168

AN:

1461440

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

726984

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00505

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000171

AC:

AN:

151982

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00606

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000202

Hom.:

Bravo

AF:

0.000132

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000214

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3474

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Feb 16, 2023

The c.767G>A (p.R256K) alteration is located in exon 5 (coding exon 5) of the ADPRHL1 gene. This alteration results from a G to A substitution at nucleotide position 767, causing the arginine (R) at amino acid position 256 to be replaced by a lysine (K). 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

0.16

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.050

T;.;T;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

D;T;D;D

M_CAP

Benign

0.034

MetaRNN

Benign

0.011

T;T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Pathogenic

3.4

.;.;M;.

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-2.8

.;D;D;D

REVEL

Benign

0.16

Sift

Uncertain

0.0070

.;D;D;D

Sift4G

Uncertain

0.022

D;D;D;D

Polyphen

0.78

.;.;P;.

Vest4

0.45

MVP

0.61

MPC

0.18

ClinPred

0.24

GERP RS

5.2

Varity_R

0.63

gMVP

0.76

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