rs12769430

Variant names:

• chr10-124552819-A-G
• rs12769430
• NM_022126.4:c.716+35548A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LHPP	NM_022126.4	c.716+35548A>G		intron_variant	Intron 6 of 6	ENST00000368842.10	NP_071409.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHPP	ENST00000368842.10	c.716+35548A>G		intron_variant	Intron 6 of 6	1	NM_022126.4	ENSP00000357835.5
LHPP	ENST00000368839.1	c.624+54691A>G		intron_variant	Intron 5 of 5	1		ENSP00000357832.1
LHPP	ENST00000482963.1	n.165+6630A>G		intron_variant	Intron 1 of 2	2
LHPP	ENST00000493240.1	n.206+6630A>G		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.184 AC: 7626 AN: 41542

American (AMR) AF: 0.418 AC: 6381 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1569 AN: 3470

East Asian (EAS) AF: 0.246 AC: 1275 AN: 5180

South Asian (SAS) AF: 0.303 AC: 1462 AN: 4828

European-Finnish (FIN) AF: 0.505 AC: 5345 AN: 10578

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35154 AN: 67992

Other (OTH) AF: 0.404 AC: 852 AN: 2110

Alfa AF: 0.488 Hom.: 9611

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
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12769430; hg19: chr10-126241388;