8-63035706-C-A

Variant names:

• chr8-63035706-C-A
• NM_003878.3:c.174G>T
• GGH p.Ala58Ala

Variant summary

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

The NM_003878.3(GGH):​c.174G>T​(p.Ala58Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A58A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GGH NM_003878.3 synonymous
• 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: 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=-0.21).
• BP7: Synonymous conserved (PhyloP=1.23 with no splicing effect.

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.174G>T	p.Ala58Ala	synonymous	Exon 2 of 9	NP_003869.1	Q92820
	GGH	NM_001410926.1		c.174G>T	p.Ala58Ala	synonymous	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.174G>T	p.Ala58Ala	synonymous	Exon 2 of 9	ENSP00000260118.6	Q92820
	GGH	ENST00000899637.1		c.174G>T	p.Ala58Ala	synonymous	Exon 2 of 10	ENSP00000569696.1
	GGH	ENST00000899635.1		c.174G>T	p.Ala58Ala	synonymous	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
BayesDel_noAF	Benign	-0.21
CADD	Benign	7.2
DANN	Benign	0.60
PhyloP100		1.2
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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: chr8-63948265;