22-24586240-GTG-ATA

Variant names:

• chr22-24586240-GTG-ATA
• NM_207644.3:c.592_594delCACinsTAT
• LRRC75B p.His198Tyr

Variant summary

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

The NM_207644.3(LRRC75B):​c.592_594delCACinsTAT​(p.His198Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LRRC75B NM_207644.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 0 publications found

Genes affected

LRRC75B (HGNC:33155): (leucine rich repeat containing 75B) Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286070 (HGNC:):

GGT1 (HGNC:4250): (gamma-glutamyltransferase 1) The enzyme encoded by this gene is a type I gamma-glutamyltransferase that catalyzes the transfer of the glutamyl moiety of glutathione to a variety of amino acids and dipeptide acceptors. The enzyme is composed of a heavy chain and a light chain, which are derived from a single precursor protein. It is expressed in tissues involved in absorption and secretion and may contribute to the etiology of diabetes and other metabolic disorders. Multiple alternatively spliced variants have been identified. There are a number of related genes present on chromosomes 20 and 22, and putative pseudogenes for this gene on chromosomes 2, 13, and 22. [provided by RefSeq, Jan 2014]

GGT1 Gene-Disease associations (from GenCC):

• gamma-glutamyl transpeptidase deficiency

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207644.3. 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
	LRRC75B	NM_207644.3	MANE Select	c.592_594delCACinsTAT	p.His198Tyr	missense	N/A	NP_997527.2	Q2VPJ9-1
	GGT1	NM_013430.3		c.-429+2432_-429+2434delGTGinsATA		intron	N/A	NP_038347.2	P19440-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC75B	ENST00000318753.13	TSL:1 MANE Select	c.592_594delCACinsTAT	p.His198Tyr	missense	N/A	ENSP00000320520.8	Q2VPJ9-1
	ENSG00000286070	ENST00000652248.1		n.*167+2432_*167+2434delGTGinsATA		intron	N/A	ENSP00000499210.1
	LRRC75B	ENST00000935984.1		c.985_987delCACinsTAT	p.His329Tyr	missense	N/A	ENSP00000606043.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-24982208;