10-124461875-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022126.4(LHPP):​c.13G>T​(p.Gly5Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G5S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LHPP NM_022126.4 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15599474).

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>T	p.Gly5Cys	missense	Exon 1 of 7	NP_071409.3
	LHPP	NM_001318332.2		c.13G>T	p.Gly5Cys	missense	Exon 1 of 6	NP_001305261.1	Q5T1Z0
	LHPP	NM_001167880.2		c.13G>T	p.Gly5Cys	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>T	p.Gly5Cys	missense	Exon 1 of 7	ENSP00000357835.5	Q9H008-1
	LHPP	ENST00000368839.1	TSL:1	c.13G>T	p.Gly5Cys	missense	Exon 1 of 6	ENSP00000357832.1	Q9H008-2
	LHPP	ENST00000890879.1		c.13G>T	p.Gly5Cys	missense	Exon 1 of 7	ENSP00000560938.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 44126 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1105162 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 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: 0.00 AC: 0 AN: 929810

Other (OTH) AF: 0.00 AC: 0 AN: 43826

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0078	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.1
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.042
Sift	Benign	0.18	T
Sift4G	Benign	0.15	T
Polyphen		0.91	P
Vest4		0.21
MutPred		0.51		Loss of disorder (P = 0.0044)
MVP		0.36
MPC		0.20
ClinPred		0.34	T
GERP RS		2.5
PromoterAI		-0.0031	Neutral
Varity_R		0.22
gMVP		0.53
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;