GGH p.Ala58Ala

Variant names:

• chr8-63035705-A-A
• NM_003878.3:c.

Your query was ambiguous. Multiple possible variants found:

• chr8-63035706--
• chr8-63035706-C-A
• chr8-63035706-C-G
• chr8-63035706-C-T

Variant summary

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

The NM_003878.3(GGH):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GGH NM_003878.3 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 0 publications found

Genes affected

GGH (HGNC:4248): (gamma-glutamyl hydrolase) This gene catalyzes the hydrolysis of folylpoly-gamma-glutamates and antifolylpoly-gamma-glutamates by the removal of gamma-linked polyglutamates and glutamate. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003878.3. 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
	GGH	NM_003878.3	MANE Select	c.		exon_region	Exon 2 of 9	NP_003869.1	Q92820
	GGH	NM_001410926.1		c.		exon_region	Exon 2 of 8	NP_001397855.1	A0A7I2V5X9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGH	ENST00000260118.7	TSL:1 MANE Select	c.		exon_region	Exon 2 of 9	ENSP00000260118.6	Q92820
	GGH	ENST00000899637.1		c.		exon_region	Exon 2 of 10	ENSP00000569696.1
	GGH	ENST00000899635.1		c.		exon_region	Exon 2 of 9	ENSP00000569694.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

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: chr8-63948264;