Variant 13-113424234-C-T 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.890G>A(p.Arg297Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000397 in 1,612,822 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

ADPRHL1
NM_001394807.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.98

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:

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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
ADPRHL1	NM_001394807.1 linkuse as main transcript	c.890G>A	p.Arg297Gln	missense_variant	6/8	ENST00000612156.3	NP_001381736.1
ADPRHL1	NM_138430.5 linkuse as main transcript	c.890G>A	p.Arg297Gln	missense_variant	6/7		NP_612439.2
ADPRHL1	NM_199162.3 linkuse as main transcript	c.644G>A	p.Arg215Gln	missense_variant	6/7		NP_954631.1
ADPRHL1	XM_047430086.1 linkuse as main transcript	c.644G>A	p.Arg215Gln	missense_variant	6/8		XP_047286042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADPRHL1	ENST00000612156.3 linkuse as main transcript	c.890G>A	p.Arg297Gln	missense_variant	6/8	5	NM_001394807.1	ENSP00000489048
ADPRHL1	ENST00000375418.8 linkuse as main transcript	c.890G>A	p.Arg297Gln	missense_variant	6/7	1		ENSP00000364567	P1	Q8NDY3-1
ADPRHL1	ENST00000356501.8 linkuse as main transcript	c.644G>A	p.Arg215Gln	missense_variant	6/7	1		ENSP00000348894		Q8NDY3-2

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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:

0.0000600

AC:

AN:

249956

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

135548

show subpopulations

Gnomad AFR exome

AF:

0.000372

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000711

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1460536

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

726560

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000112

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000965

Hom.:

Bravo

AF:

0.000147

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000660

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

Oct 27, 2023

The c.890G>A (p.R297Q) alteration is located in exon 6 (coding exon 6) of the ADPRHL1 gene. This alteration results from a G to A substitution at nucleotide position 890, causing the arginine (R) at amino acid position 297 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

0.16

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.023

T;.;T

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Uncertain

0.091

MetaRNN

Uncertain

0.56

D;D;D

MetaSVM

Benign

-0.88

MutationAssessor

Pathogenic

3.3

.;.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.0

.;D;D

REVEL

Benign

0.28

Sift

Benign

0.067

.;T;D

Sift4G

Uncertain

0.011

D;T;T

Polyphen

1.0

.;.;D

Vest4

0.67

MVP

0.48

MPC

0.44

ClinPred

0.78

GERP RS

3.0

Varity_R

0.26

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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