NM_022126.4:c.716+29662A>G

Variant names:

• chr10-124546933-A-G
• rs7073611
• NM_022126.4:c.716+29662A>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+29662A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,004 control chromosomes in the GnomAD database, including 1,086 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 0.10 (1086 hom., cov: 33)
• Consequence: LHPP NM_022126.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.983
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022126.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHPP	NM_022126.4	MANE Select	c.716+29662A>G		intron	N/A	NP_071409.3
	LHPP	NM_001167880.2		c.624+48805A>G		intron	N/A	NP_001161352.1	Q9H008-2
	LHPP	NM_001318331.2		c.467+58358A>G		intron	N/A	NP_001305260.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHPP	ENST00000368842.10	TSL:1 MANE Select	c.716+29662A>G		intron	N/A	ENSP00000357835.5	Q9H008-1
	LHPP	ENST00000368839.1	TSL:1	c.624+48805A>G		intron	N/A	ENSP00000357832.1	Q9H008-2
	LHPP	ENST00000890879.1		c.625-6998A>G		intron	N/A	ENSP00000560938.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15810 AN: 151886 Hom.: 1087 Cov.: 33

Gnomad AFR AF: 0.0255

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0958

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.104 AC: 15804 AN: 152004 Hom.: 1086 Cov.: 33 AF XY: 0.104 AC XY: 7757 AN XY: 74312

African (AFR) AF: 0.0254 AC: 1055 AN: 41460

American (AMR) AF: 0.0956 AC: 1461 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 593 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5188

South Asian (SAS) AF: 0.114 AC: 546 AN: 4796

European-Finnish (FIN) AF: 0.141 AC: 1486 AN: 10538

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10328 AN: 67958

Other (OTH) AF: 0.109 AC: 230 AN: 2110

Alfa AF: 0.123 Hom.: 861

Bravo AF: 0.0932

Asia WGS AF: 0.0400 AC: 138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.078
DANN	Benign	0.35
PhyloP100		-0.98
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: rs7073611; hg19: chr10-126235502;