NM_022126.4:c.19C>A

Variant names:

• chr10-124461881-C-A
• rs767909716
• NM_022126.4:c.19C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_022126.4(LHPP):​c.19C>A​(p.Arg7Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,902 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LHPP NM_022126.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.956
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP7: Synonymous conserved (PhyloP=0.956 with no splicing effect.

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.19C>A	p.Arg7Arg	synonymous	Exon 1 of 7	NP_071409.3
	LHPP	NM_001318332.2		c.19C>A	p.Arg7Arg	synonymous	Exon 1 of 6	NP_001305261.1	Q5T1Z0
	LHPP	NM_001167880.2		c.19C>A	p.Arg7Arg	synonymous	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.19C>A	p.Arg7Arg	synonymous	Exon 1 of 7	ENSP00000357835.5	Q9H008-1
	LHPP	ENST00000368839.1	TSL:1	c.19C>A	p.Arg7Arg	synonymous	Exon 1 of 6	ENSP00000357832.1	Q9H008-2
	LHPP	ENST00000890879.1		c.19C>A	p.Arg7Arg	synonymous	Exon 1 of 7	ENSP00000560938.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151902 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1105560 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 525640

African (AFR) AF: 0.00 AC: 0 AN: 23734

American (AMR) AF: 0.00 AC: 0 AN: 11088

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13992

East Asian (EAS) AF: 0.00 AC: 0 AN: 28096

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30198

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2994

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 929992

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

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151902 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74198

African (AFR) AF: 0.00 AC: 0 AN: 41394

American (AMR) AF: 0.0000655 AC: 1 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67938

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	9.5
DANN	Benign	0.81
PhyloP100		0.96
PromoterAI		0.068	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=100/0	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: rs767909716; hg19: chr10-126150450;