Variant 13-113424235-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001394807.1(ADPRHL1):c.889C>T(p.Arg297Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000285 in 1,612,688 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

ADPRHL1
NM_001394807.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.71

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADPRHL1	NM_001394807.1 linkuse as main transcript	c.889C>T	p.Arg297Trp	missense_variant	6/8	ENST00000612156.3	NP_001381736.1
ADPRHL1	NM_138430.5 linkuse as main transcript	c.889C>T	p.Arg297Trp	missense_variant	6/7		NP_612439.2	Q8NDY3-1
ADPRHL1	NM_199162.3 linkuse as main transcript	c.643C>T	p.Arg215Trp	missense_variant	6/7		NP_954631.1	Q8NDY3-2
ADPRHL1	XM_047430086.1 linkuse as main transcript	c.643C>T	p.Arg215Trp	missense_variant	6/8		XP_047286042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADPRHL1	ENST00000612156.3 linkuse as main transcript	c.889C>T	p.Arg297Trp	missense_variant	6/8	5	NM_001394807.1	ENSP00000489048.1	A0A0U1RQK4
ADPRHL1	ENST00000375418.8 linkuse as main transcript	c.889C>T	p.Arg297Trp	missense_variant	6/7	1		ENSP00000364567.3	Q8NDY3-1
ADPRHL1	ENST00000356501.8 linkuse as main transcript	c.643C>T	p.Arg215Trp	missense_variant	6/7	1		ENSP00000348894.4	Q8NDY3-2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000960

AC:

AN:

249918

Hom.:

AF XY:

0.0000812

AC XY:

AN XY:

135532

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00120

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000281

AC:

AN:

1460532

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

726566

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000579

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000982

ExAC

AF:

0.000107

AC:

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

May 17, 2023

The c.889C>T (p.R297W) alteration is located in exon 6 (coding exon 6) of the ADPRHL1 gene. This alteration results from a C to T substitution at nucleotide position 889, causing the arginine (R) at amino acid position 297 to be replaced by a tryptophan (W). 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

0.15

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.048

T;.;T

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.071

MetaRNN

Uncertain

0.65

D;D;D

MetaSVM

Benign

-0.64

MutationAssessor

Pathogenic

3.3

.;.;M

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-6.6

.;D;D

REVEL

Uncertain

0.43

Sift

Uncertain

0.0010

.;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.75

MutPred

0.80

Loss of disorder (P = 0.0449);.;Loss of disorder (P = 0.0449);

MVP

0.67

MPC

0.13

ClinPred

0.58

GERP RS

4.8

Varity_R

0.44

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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