rs12773846

Positions:

• chr10-124587345-G-A
• chr10-124587345-G-C

Variant summary

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

The NM_022126.4(LHPP):​c.717-25919G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,626 control chromosomes in the GnomAD database, including 8,394 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 0.33 (8394 hom., cov: 28)
• Consequence: LHPP NM_022126.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21

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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHPP	NM_022126.4	c.717-25919G>A		intron_variant		ENST00000368842.10	NP_071409.3
LHPP	NM_001167880.2	c.625-25919G>A		intron_variant			NP_001161352.1
LHPP	NM_001318331.2	c.468-25919G>A		intron_variant			NP_001305260.1
LHPP	XM_005270026.4	c.832-25919G>A		intron_variant			XP_005270083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHPP	ENST00000368842.10	c.717-25919G>A		intron_variant		1	NM_022126.4	ENSP00000357835	P1
LHPP	ENST00000368839.1	c.625-25919G>A		intron_variant		1		ENSP00000357832
LHPP	ENST00000482963.1	n.166-25919G>A		intron_variant, non_coding_transcript_variant		2
LHPP	ENST00000493240.1	n.207-25919G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49253 AN: 151508 Hom.: 8380 Cov.: 28

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.325 AC: 49295 AN: 151626 Hom.: 8394 Cov.: 28 AF XY: 0.324 AC XY: 24000 AN XY: 74078

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.322

Alfa AF: 0.302 Hom.: 13786

Bravo AF: 0.318

Asia WGS AF: 0.324 AC: 1126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.045
DANN	Benign	0.71

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: rs12773846; hg19: chr10-126275914;