Variant 10-124484332-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The ENST00000368842.10(LHPP):c.313+6C>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0083 in 1,608,110 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 4 hom., cov: 30)

Exomes 𝑓: 0.0086 ( 75 hom. )

Consequence

LHPP
ENST00000368842.10 splice_donor_region, intron

Scores

Splicing: ADA: 0.0002298

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.563

Variant links:

Genes affected

LHPP (HGNC:30042): (phospholysine phosphohistidine inorganic pyrophosphate phosphatase) Enables inorganic diphosphatase activity and protein homodimerization activity. Involved in phosphate-containing compound metabolic process. Located in cytosol and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

LHPP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 10-124484332-C-A is Benign according to our data. Variant chr10-124484332-C-A is described in ClinVar as [Benign]. Clinvar id is 770397.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHPP	NM_022126.4 linkuse as main transcript	c.313+6C>A		splice_donor_region_variant, intron_variant		ENST00000368842.10	NP_071409.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
LHPP	ENST00000368842.10 linkuse as main transcript	c.313+6C>A	splice_donor_region_variant, intron_variant	1	NM_022126.4	ENSP00000357835	P1	Q9H008-1
LHPP	ENST00000368839.1 linkuse as main transcript	c.313+6C>A	splice_donor_region_variant, intron_variant	1		ENSP00000357832		Q9H008-2
LHPP	ENST00000392757.8 linkuse as main transcript	c.313+6C>A	splice_donor_region_variant, intron_variant	3		ENSP00000376512

Frequencies

GnomAD3 genomes

AF:

0.00580

AC:

882

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00786

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00622

Gnomad FIN

AF:

0.00603

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00807

Gnomad OTH

AF:

0.00911

GnomAD3 exomes

AF:

0.00624

AC:

1558

AN:

249786

Hom.:

AF XY:

0.00653

AC XY:

883

AN XY:

135262

show subpopulations

Gnomad AFR exome

AF:

0.000866

Gnomad AMR exome

AF:

0.00424

Gnomad ASJ exome

AF:

0.0119

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00482

Gnomad FIN exome

AF:

0.00704

Gnomad NFE exome

AF:

0.00822

Gnomad OTH exome

AF:

0.00871

GnomAD4 exome

AF:

0.00856

AC:

12461

AN:

1455856

Hom.:

Cov.:

AF XY:

0.00846

AC XY:

6118

AN XY:

722994

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.00462

Gnomad4 ASJ exome

AF:

0.0114

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00498

Gnomad4 FIN exome

AF:

0.00629

Gnomad4 NFE exome

AF:

0.00960

Gnomad4 OTH exome

AF:

0.00825

GnomAD4 genome

AF:

0.00579

AC:

882

AN:

152254

Hom.:

Cov.:

AF XY:

0.00599

AC XY:

446

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00140

Gnomad4 AMR

AF:

0.00785

Gnomad4 ASJ

AF:

0.0110

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00643

Gnomad4 FIN

AF:

0.00603

Gnomad4 NFE

AF:

0.00807

Gnomad4 OTH

AF:

0.00901

Alfa

AF:

0.00616

Hom.:

Bravo

AF:

0.00541

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00916

EpiControl

AF:

0.00919

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00023

dbscSNV1_RF

Benign

0.0

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