rs11545077

Variant names:

• chr8-63038678-C-A
• rs11545077
• NM_003878.3:c.91G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-63038678-C-A
• chr8-63038678-C-G
• chr8-63038678-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003878.3(GGH):​c.91G>T​(p.Ala31Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,377,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: GGH NM_003878.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 31 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03947848).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGH	NM_003878.3	MANE Select	c.91G>T	p.Ala31Ser	missense	Exon 1 of 9	NP_003869.1
	GGH	NM_001410926.1		c.91G>T	p.Ala31Ser	missense	Exon 1 of 8	NP_001397855.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGH	ENST00000260118.7	TSL:1 MANE Select	c.91G>T	p.Ala31Ser	missense	Exon 1 of 9	ENSP00000260118.6
	GGH	ENST00000518113.2	TSL:3	c.91G>T	p.Ala31Ser	missense	Exon 1 of 8	ENSP00000504520.1
	GGH	ENST00000677482.1		c.91G>T	p.Ala31Ser	missense	Exon 1 of 9	ENSP00000504590.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000491 AC: 1 AN: 203866 AF XY: 0.00000889

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1377698 Hom.: 0 Cov.: 29 AF XY: 0.00000146 AC XY: 1 AN XY: 684502

African (AFR) AF: 0.00 AC: 0 AN: 29978

American (AMR) AF: 0.00 AC: 0 AN: 39836

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23880

East Asian (EAS) AF: 0.0000281 AC: 1 AN: 35534

South Asian (SAS) AF: 0.0000129 AC: 1 AN: 77348

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5432

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1061418

Other (OTH) AF: 0.00 AC: 0 AN: 56016

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000830 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.15
DANN	Benign	0.87
DEOGEN2	Benign	0.16	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.2	N
PhyloP100		-1.3
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.038
Sift	Benign	0.50	T
Sift4G	Benign	0.86	T
Polyphen		0.0	B
Vest4		0.018
MutPred		0.31		Loss of sheet (P = 3e-04)
MVP		0.31
MPC		0.085
ClinPred		0.030	T
GERP RS		-8.0
PromoterAI		-0.043	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.25
gMVP		0.40
Mutation Taster		=95/5	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: rs11545077; hg19: chr8-63951237;