chr10-124484332-C-A

Variant names:

• chr10-124484332-C-A
• rs112299803
• NM_022126.4:c.313+6C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_022126.4(LHPP):​c.313+6C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0083 in 1,608,110 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (4 hom., cov: 30)
  • Exomes 𝑓: 0.0086 (75 hom.)
• Consequence: LHPP NM_022126.4 splice_region, intron
• Scores: Splicing: ADA: 0.0002298
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.563
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 10-124484332-C-A is Benign according to our data. Variant chr10-124484332-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 770397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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.313+6C>A		splice_region intron	N/A	NP_071409.3
	LHPP	NM_001318332.2		c.313+6C>A		splice_region intron	N/A	NP_001305261.1	Q5T1Z0
	LHPP	NM_001167880.2		c.313+6C>A		splice_region intron	N/A	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.313+6C>A		splice_region intron	N/A	ENSP00000357835.5	Q9H008-1
	LHPP	ENST00000368839.1	TSL:1	c.313+6C>A		splice_region intron	N/A	ENSP00000357832.1	Q9H008-2
	LHPP	ENST00000890879.1		c.313+6C>A		splice_region intron	N/A	ENSP00000560938.1

Frequencies

GnomAD3 genomes AF: 0.00580 AC: 882 AN: 152136 Hom.: 4 Cov.: 30

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00786

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00622

Gnomad FIN AF: 0.00603

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00807

Gnomad OTH AF: 0.00911

GnomAD2 exomes AF: 0.00624 AC: 1558 AN: 249786 AF XY: 0.00653

Gnomad AFR exome AF: 0.000866

Gnomad AMR exome AF: 0.00424

Gnomad ASJ exome AF: 0.0119

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00704

Gnomad NFE exome AF: 0.00822

Gnomad OTH exome AF: 0.00871

GnomAD4 exome AF: 0.00856 AC: 12461 AN: 1455856 Hom.: 75 Cov.: 33 AF XY: 0.00846 AC XY: 6118 AN XY: 722994

African (AFR) AF: 0.00117 AC: 39 AN: 33370

American (AMR) AF: 0.00462 AC: 206 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.0114 AC: 298 AN: 26056

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39514

South Asian (SAS) AF: 0.00498 AC: 429 AN: 86124

European-Finnish (FIN) AF: 0.00629 AC: 334 AN: 53114

Middle Eastern (MID) AF: 0.00495 AC: 28 AN: 5656

European-Non Finnish (NFE) AF: 0.00960 AC: 10630 AN: 1107322

Other (OTH) AF: 0.00825 AC: 496 AN: 60102

GnomAD4 genome AF: 0.00579 AC: 882 AN: 152254 Hom.: 4 Cov.: 30 AF XY: 0.00599 AC XY: 446 AN XY: 74438

African (AFR) AF: 0.00140 AC: 58 AN: 41556

American (AMR) AF: 0.00785 AC: 120 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 38 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00643 AC: 31 AN: 4820

European-Finnish (FIN) AF: 0.00603 AC: 64 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00807 AC: 549 AN: 68010

Other (OTH) AF: 0.00901 AC: 19 AN: 2108

Alfa AF: 0.00616 Hom.: 1

Bravo AF: 0.00541

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00916

EpiControl AF: 0.00919

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.85
PhyloP100		0.56
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00023
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.010		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: rs112299803; hg19: chr10-126172901;