rs12569498

Positions:

• chr10-124496419-T-C
• chr10-124496419-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000368842.10(LHPP):​c.468-542T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LHPP ENST00000368842.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHPP	NM_022126.4	c.468-542T>C		intron_variant		ENST00000368842.10	NP_071409.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHPP	ENST00000368842.10	c.468-542T>C		intron_variant		1	NM_022126.4	ENSP00000357835	P1
LHPP	ENST00000368839.1	c.468-542T>C		intron_variant		1		ENSP00000357832
LHPP	ENST00000392757.8	c.468-542T>C		intron_variant		3		ENSP00000376512
LHPP	ENST00000481452.1	n.114-542T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.9
DANN	Benign	0.77

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

Other links and lift over

dbSNP: rs12569498; hg19: chr10-126184988;