chr13-113405457-G-A

Position:

• chr13-113405457-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001394807.1(ADPRHL1):​c.3825C>T​(p.Ser1275=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,231,928 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (1 hom., cov: 34)
  • Exomes 𝑓: 0.00020 (2 hom.)
• Consequence: ADPRHL1 NM_001394807.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.74

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 Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 13-113405457-G-A is Benign according to our data. Variant chr13-113405457-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2644003.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.74 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADPRHL1	NM_001394807.1	c.3825C>T	p.Ser1275=	synonymous_variant	8/8	ENST00000612156.3	NP_001381736.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADPRHL1	ENST00000612156.3	c.3825C>T	p.Ser1275=	synonymous_variant	8/8	5	NM_001394807.1	ENSP00000489048
ADPRHL1	ENST00000682618.1	c.2733C>T	p.Ser911=	synonymous_variant	2/2			ENSP00000506851

Frequencies

GnomAD3 genomes AF: 0.000296 AC: 45 AN: 152230 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.000196 AC: 212 AN: 1079578 Hom.: 2 Cov.: 72 AF XY: 0.000200 AC XY: 102 AN XY: 509644

Gnomad4 AFR exome AF: 0.000174

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00215

Gnomad4 FIN exome AF: 0.0000948

Gnomad4 NFE exome AF: 0.000136

Gnomad4 OTH exome AF: 0.000595

GnomAD4 genome AF: 0.000295 AC: 45 AN: 152350 Hom.: 1 Cov.: 34 AF XY: 0.000389 AC XY: 29 AN XY: 74504

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00331

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.0000693 Hom.: 0

Bravo AF: 0.000185

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

ADPRHL1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.57
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs139448172; hg19: chr13-114059772;