Variant 10-124461978-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_022126.4(LHPP):c.116C>T(p.Ala39Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 1,217,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

LHPP
NM_022126.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.93

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.889

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LHPP	NM_022126.4 linkuse as main transcript	c.116C>T	p.Ala39Val	missense_variant	1/7	ENST00000368842.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHPP	ENST00000368842.10 linkuse as main transcript	c.116C>T	p.Ala39Val	missense_variant	1/7	1	NM_022126.4	P1	Q9H008-1
LHPP	ENST00000368839.1 linkuse as main transcript	c.116C>T	p.Ala39Val	missense_variant	1/6	1			Q9H008-2
LHPP	ENST00000392757.8 linkuse as main transcript	c.116C>T	p.Ala39Val	missense_variant	1/6	3

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151770

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:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000563

AC:

AN:

1065962

Hom.:

Cov.:

AF XY:

0.00000199

AC XY:

AN XY:

503494

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000661

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151770

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74148

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:

0.0000295

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

Dec 20, 2021

The c.116C>T (p.A39V) alteration is located in exon 1 (coding exon 1) of the LHPP gene. This alteration results from a C to T substitution at nucleotide position 116, causing the alanine (A) at amino acid position 39 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

Pathogenic

0.71

BayesDel_addAF

Uncertain

0.015

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Pathogenic

1.0

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Benign

0.32

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Pathogenic

0.48

MetaRNN

Pathogenic

0.89

D;D;D

MetaSVM

Benign

-0.75

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-3.2

D;D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0080

D;D;D

Sift4G

Uncertain

0.0080

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.59

MutPred

0.76

Gain of MoRF binding (P = 0.1182);Gain of MoRF binding (P = 0.1182);Gain of MoRF binding (P = 0.1182);

MVP

0.19

MPC

0.53

ClinPred

1.0

GERP RS

4.3

Varity_R

0.98

gMVP

0.70

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