10-124496419-T-G

Variant names:

• chr10-124496419-T-G
• rs12569498
• NM_022126.4:c.468-542T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022126.4(LHPP):​c.468-542T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 152,038 control chromosomes in the GnomAD database, including 21,980 homozygotes. 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: 𝑓 0.53 (21980 hom., cov: 33)
• Consequence: LHPP NM_022126.4 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHPP	NM_022126.4	c.468-542T>G		intron_variant	Intron 3 of 6	ENST00000368842.10	NP_071409.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHPP	ENST00000368842.10	c.468-542T>G		intron_variant	Intron 3 of 6	1	NM_022126.4	ENSP00000357835.5
LHPP	ENST00000368839.1	c.468-542T>G		intron_variant	Intron 3 of 5	1		ENSP00000357832.1
LHPP	ENST00000392757.8	c.468-542T>G		intron_variant	Intron 3 of 5	3		ENSP00000376512.4
LHPP	ENST00000481452.1	n.114-542T>G		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80924 AN: 151920 Hom.: 21977 Cov.: 33

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.532 AC: 80954 AN: 152038 Hom.: 21980 Cov.: 33 AF XY: 0.538 AC XY: 40002 AN XY: 74316

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.678

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.556

Alfa AF: 0.550 Hom.: 33173

Bravo AF: 0.518

Asia WGS AF: 0.526 AC: 1829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.8
DANN	Benign	0.79

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;