10-124461875-G-A

Variant names:

• chr10-124461875-G-A
• rs762295411
• NM_022126.4:c.13G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022126.4(LHPP):​c.13G>A​(p.Gly5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,257,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: LHPP NM_022126.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.12
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046429962).

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.13G>A	p.Gly5Ser	missense	Exon 1 of 7	NP_071409.3
	LHPP	NM_001318332.2		c.13G>A	p.Gly5Ser	missense	Exon 1 of 6	NP_001305261.1	Q5T1Z0
	LHPP	NM_001167880.2		c.13G>A	p.Gly5Ser	missense	Exon 1 of 6	NP_001161352.1	Q9H008-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHPP	ENST00000368842.10	TSL:1 MANE Select	c.13G>A	p.Gly5Ser	missense	Exon 1 of 7	ENSP00000357835.5	Q9H008-1
	LHPP	ENST00000368839.1	TSL:1	c.13G>A	p.Gly5Ser	missense	Exon 1 of 6	ENSP00000357832.1	Q9H008-2
	LHPP	ENST00000890879.1		c.13G>A	p.Gly5Ser	missense	Exon 1 of 7	ENSP00000560938.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151958 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000227 AC: 1 AN: 44126 AF XY: 0.0000413

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000408

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000217 AC: 24 AN: 1105164 Hom.: 0 Cov.: 33 AF XY: 0.0000228 AC XY: 12 AN XY: 525432

African (AFR) AF: 0.00 AC: 0 AN: 23744

American (AMR) AF: 0.00 AC: 0 AN: 11090

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13970

East Asian (EAS) AF: 0.00 AC: 0 AN: 28120

South Asian (SAS) AF: 0.00 AC: 0 AN: 21638

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2992

European-Non Finnish (NFE) AF: 0.0000258 AC: 24 AN: 929810

Other (OTH) AF: 0.00 AC: 0 AN: 43828

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151958 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74236

African (AFR) AF: 0.00 AC: 0 AN: 41398

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67958

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000970 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.6
DANN	Benign	0.92
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.1
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.021
Sift	Benign	0.54	T
Sift4G	Benign	0.68	T
Polyphen		0.035	B
Vest4		0.13
MutPred		0.32		Gain of glycosylation at P3 (P = 0.0649)
MVP		0.030
MPC		0.19
ClinPred		0.048	T
GERP RS		2.5
PromoterAI		-0.051	Neutral
Varity_R		0.085
gMVP		0.48
Mutation Taster		=75/25	polymorphism

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: rs762295411; hg19: chr10-126150444;