NM_022126.4:c.717-6278C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 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.717-6278C>T		intron	N/A	NP_071409.3
	LHPP	NM_001167880.2		c.625-6278C>T		intron	N/A	NP_001161352.1	Q9H008-2
	LHPP	NM_001318331.2		c.468-6278C>T		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.717-6278C>T		intron	N/A	ENSP00000357835.5	Q9H008-1
	LHPP	ENST00000368839.1	TSL:1	c.625-6278C>T		intron	N/A	ENSP00000357832.1	Q9H008-2
	LHPP	ENST00000486535.1	TSL:1	n.316+1471C>T		intron	N/A

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

African (AFR) AF: 0.628 AC: 26058 AN: 41470

American (AMR) AF: 0.556 AC: 8499 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2186 AN: 3468

East Asian (EAS) AF: 0.611 AC: 3155 AN: 5164

South Asian (SAS) AF: 0.575 AC: 2774 AN: 4822

European-Finnish (FIN) AF: 0.771 AC: 8174 AN: 10596

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43665 AN: 67972

Other (OTH) AF: 0.616 AC: 1300 AN: 2112

Alfa AF: 0.629 Hom.: 25032

Bravo AF: 0.621

Asia WGS AF: 0.593 AC: 2064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.70
PhyloP100		-0.55
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: rs7923479; hg19: chr10-126295555;