13-113428997-G-T

Position:

• chr13-113428997-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001394807.1(ADPRHL1):​c.601C>A​(p.Pro201Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 5.98

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.941

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADPRHL1	NM_001394807.1	c.601C>A	p.Pro201Thr	missense_variant	4/8	ENST00000612156.3	NP_001381736.1
ADPRHL1	NM_138430.5	c.601C>A	p.Pro201Thr	missense_variant	4/7		NP_612439.2
ADPRHL1	NM_199162.3	c.355C>A	p.Pro119Thr	missense_variant	4/7		NP_954631.1
ADPRHL1	XM_047430086.1	c.355C>A	p.Pro119Thr	missense_variant	4/8		XP_047286042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADPRHL1	ENST00000612156.3	c.601C>A	p.Pro201Thr	missense_variant	4/8	5	NM_001394807.1	ENSP00000489048
ADPRHL1	ENST00000375418.8	c.601C>A	p.Pro201Thr	missense_variant	4/7	1		ENSP00000364567	P1
ADPRHL1	ENST00000356501.8	c.355C>A	p.Pro119Thr	missense_variant	4/7	1		ENSP00000348894
ADPRHL1	ENST00000413169.2	c.355C>A	p.Pro119Thr	missense_variant	4/5	3		ENSP00000416213

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

Jan 10, 2023

The c.601C>A (p.P201T) alteration is located in exon 4 (coding exon 4) of the ADPRHL1 gene. This alteration results from a C to A substitution at nucleotide position 601, causing the proline (P) at amino acid position 201 to be replaced by a threonine (T). 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	0.18
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T;.;T;.
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	T;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.94	D;D;D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.8	.;.;M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-6.8	.;D;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0020	.;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D
Polyphen		0.89	.;.;P;.
Vest4		0.36
MutPred		0.76		Gain of MoRF binding (P = 0.047);.;Gain of MoRF binding (P = 0.047);.;
MVP		0.43
MPC		0.25
ClinPred		0.95	D
GERP RS		5.2
Varity_R		0.70
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-114083312;