10-124484332-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_022126.4(LHPP):c.313+6C>A variant causes a splice donor 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. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0058 (4 hom., cov: 30)
  • Exomes 𝑓: 0.0086 (75 hom.)
• Consequence: LHPP NM_022126.4 splice_donor_region, intron
• Scores: Splicing: ADA: 0.0002298
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.563

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

Verdict is Benign. Variant got -8 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]. Clinvar id is 770397.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LHPP	NM_022126.4	c.313+6C>A		splice_donor_region_variant, intron_variant		ENST00000368842.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHPP	ENST00000368842.10	c.313+6C>A		splice_donor_region_variant, intron_variant		1	NM_022126.4	P1
LHPP	ENST00000368839.1	c.313+6C>A		splice_donor_region_variant, intron_variant		1
LHPP	ENST00000392757.8	c.313+6C>A		splice_donor_region_variant, intron_variant		3

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

GnomAD3 exomes AF: 0.00624 AC: 1558 AN: 249786 Hom.: 4 AF XY: 0.00653 AC XY: 883 AN XY: 135262

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 SAS exome AF: 0.00482

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

Gnomad4 AFR exome AF: 0.00117

Gnomad4 AMR exome AF: 0.00462

Gnomad4 ASJ exome AF: 0.0114

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00498

Gnomad4 FIN exome AF: 0.00629

Gnomad4 NFE exome AF: 0.00960

Gnomad4 OTH exome AF: 0.00825

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

Gnomad4 AFR AF: 0.00140

Gnomad4 AMR AF: 0.00785

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00643

Gnomad4 FIN AF: 0.00603

Gnomad4 NFE AF: 0.00807

Gnomad4 OTH AF: 0.00901

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 31, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	13
Dann	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs112299803; hg19: chr10-126172901;