8-63026205-G-C

Variant names:

• chr8-63026205-G-C
• rs11545078
• NM_003878.3:c.452C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003878.3(GGH):​c.452C>G​(p.Thr151Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GGH NM_003878.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.18
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13500488).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGH	NM_003878.3	c.452C>G	p.Thr151Ser	missense_variant	Exon 5 of 9	ENST00000260118.7	NP_003869.1
GGH	NM_001410926.1	c.452C>G	p.Thr151Ser	missense_variant	Exon 5 of 8		NP_001397855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGH	ENST00000260118.7	c.452C>G	p.Thr151Ser	missense_variant	Exon 5 of 9	1	NM_003878.3	ENSP00000260118.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Benign	0.72
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.079
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.2
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.7	N
Sift	Benign	0.36	T
Sift4G	Benign	0.46	T
Vest4		0.060
ClinPred		0.42	T
GERP RS		5.9
PromoterAI		0.0074	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.37
gMVP		0.70
Mutation Taster		=71/29	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: rs11545078; hg19: chr8-63938764;