10-124606986-C-T

Variant names:

• chr10-124606986-C-T
• rs7923479
• NM_022126.4:c.717-6278C>T

Variant summary

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

The NM_022126.4(LHPP):​c.717-6278C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 152,096 control chromosomes in the GnomAD database, including 30,978 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 0.64 (30978 hom., cov: 33)
• Consequence: LHPP NM_022126.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHPP	NM_022126.4	c.717-6278C>T		intron_variant	Intron 6 of 6	ENST00000368842.10	NP_071409.3
LHPP	NM_001167880.2	c.625-6278C>T		intron_variant	Intron 5 of 5		NP_001161352.1
LHPP	NM_001318331.2	c.468-6278C>T		intron_variant	Intron 3 of 3		NP_001305260.1
LHPP	XM_005270026.4	c.832-6278C>T		intron_variant	Intron 7 of 7		XP_005270083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHPP	ENST00000368842.10	c.717-6278C>T		intron_variant	Intron 6 of 6	1	NM_022126.4	ENSP00000357835.5

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96580 AN: 151978 Hom.: 30958 Cov.: 33

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.635 AC: 96648 AN: 152096 Hom.: 30978 Cov.: 33 AF XY: 0.638 AC XY: 47422 AN XY: 74352

Gnomad4 AFR AF: 0.628

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.575

Gnomad4 FIN AF: 0.771

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.616

Alfa AF: 0.625 Hom.: 17134

Bravo AF: 0.621

Asia WGS AF: 0.593 AC: 2064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	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

Other links and lift over

dbSNP: rs7923479; hg19: chr10-126295555;