13-113428984-T-A

Position:

• chr13-113428984-T-A

Variant summary

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

The NM_001394807.1(ADPRHL1):​c.614A>T​(p.Glu205Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: ADPRHL1 NM_001394807.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.45

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]

ACMG classification

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	c.614A>T	p.Glu205Val	missense_variant	4/8	ENST00000612156.3	NP_001381736.1
ADPRHL1	NM_138430.5	c.614A>T	p.Glu205Val	missense_variant	4/7		NP_612439.2
ADPRHL1	NM_199162.3	c.368A>T	p.Glu123Val	missense_variant	4/7		NP_954631.1
ADPRHL1	XM_047430086.1	c.368A>T	p.Glu123Val	missense_variant	4/8		XP_047286042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADPRHL1	ENST00000612156.3	c.614A>T	p.Glu205Val	missense_variant	4/8	5	NM_001394807.1	ENSP00000489048.1
ADPRHL1	ENST00000375418.8	c.614A>T	p.Glu205Val	missense_variant	4/7	1		ENSP00000364567.3
ADPRHL1	ENST00000356501.8	c.368A>T	p.Glu123Val	missense_variant	4/7	1		ENSP00000348894.4
ADPRHL1	ENST00000413169.2	c.368A>T	p.Glu123Val	missense_variant	4/5	3		ENSP00000416213.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2022

The c.614A>T (p.E205V) alteration is located in exon 4 (coding exon 4) of the ADPRHL1 gene. This alteration results from a A to T substitution at nucleotide position 614, causing the glutamic acid (E) at amino acid position 205 to be replaced by a valine (V). 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	0.17
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T;.;T;.
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T;T;T;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.50	D;D;D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.3	.;.;M;.
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-4.1	.;D;D;D
REVEL	Benign	0.20
Sift	Benign	0.18	.;T;T;T
Sift4G	Uncertain	0.014	D;T;T;T
Polyphen		0.90	.;.;P;.
Vest4		0.49
MutPred		0.51		Gain of loop (P = 0.0166);.;Gain of loop (P = 0.0166);.;
MVP		0.48
MPC		0.17
ClinPred		0.96	D
GERP RS		5.2
Varity_R		0.44
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-114083299;