Variant 13-113422827-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001394807.1(ADPRHL1):c.1060A>G(p.Asn354Asp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000682 in 1,612,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

ADPRHL1
NM_001394807.1 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.19

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4072732).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADPRHL1	NM_001394807.1 linkuse as main transcript	c.1060A>G	p.Asn354Asp	missense_variant, splice_region_variant	7/8	ENST00000612156.3	NP_001381736.1
ADPRHL1	NM_138430.5 linkuse as main transcript	c.1060A>G	p.Lys354Glu	missense_variant	7/7		NP_612439.2	Q8NDY3-1
ADPRHL1	NM_199162.3 linkuse as main transcript	c.814A>G	p.Lys272Glu	missense_variant	7/7		NP_954631.1	Q8NDY3-2
ADPRHL1	XM_047430086.1 linkuse as main transcript	c.814A>G	p.Asn272Asp	missense_variant, splice_region_variant	7/8		XP_047286042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADPRHL1	ENST00000375418.8 linkuse as main transcript	c.1060A>G	p.Lys354Glu	missense_variant	7/7	1		ENSP00000364567.3	Q8NDY3-1
ADPRHL1	ENST00000356501.8 linkuse as main transcript	c.814A>G	p.Lys272Glu	missense_variant	7/7	1		ENSP00000348894.4	Q8NDY3-2
ADPRHL1	ENST00000612156.3 linkuse as main transcript	c.1060A>G	p.Asn354Asp	missense_variant, splice_region_variant	7/8	5	NM_001394807.1	ENSP00000489048.1	A0A0U1RQK4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1460580

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726568

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Nov 22, 2021

The c.1060A>G (p.K354E) alteration is located in exon 7 (coding exon 7) of the ADPRHL1 gene. This alteration results from a A to G substitution at nucleotide position 1060, causing the lysine (K) at amino acid position 354 to be replaced by a glutamic acid (E). 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

0.11

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0041

.;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.41

T;T

MetaSVM

Benign

-0.79

MutationAssessor

Pathogenic

3.0

.;M

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.50

N;N

REVEL

Benign

0.24

Sift

Benign

0.033

D;D

Sift4G

Uncertain

0.010

D;D

Polyphen

0.68

.;P

Vest4

0.55

MutPred

0.37

.;Loss of ubiquitination at K354 (P = 0.0023);

MVP

0.42

MPC

0.37

ClinPred

0.98

GERP RS

5.0

Varity_R

0.31

gMVP

0.46

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