rs12769430

chr10-124552819-A-G

Variant summary

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

The NM_022126.4(LHPP):c.716+35548A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 152,186 control chromosomes in the GnomAD database, including 13,647 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 0.40 (13647 hom., cov: 33)
• Consequence: LHPP NM_022126.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64

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=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LHPP	NM_022126.4	c.716+35548A>G		intron_variant		ENST00000368842.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHPP	ENST00000368842.10	c.716+35548A>G		intron_variant		1	NM_022126.4	P1
LHPP	ENST00000368839.1	c.624+54691A>G		intron_variant		1
LHPP	ENST00000482963.1	n.165+6630A>G		intron_variant, non_coding_transcript_variant		2
LHPP	ENST00000493240.1	n.206+6630A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60259 AN: 152066 Hom.: 13638 Cov.: 33

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.396 AC: 60280 AN: 152186 Hom.: 13647 Cov.: 33 AF XY: 0.393 AC XY: 29250 AN XY: 74380

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.404

Alfa AF: 0.481 Hom.: 5694

Bravo AF: 0.377

Asia WGS AF: 0.262 AC: 911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	17
Dann	Benign	0.65

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: rs12769430; hg19: chr10-126241388;