chr20-23986458-C-G

Variant names:

• chr20-23986458-C-G
• rs371694918
• NM_178311.3:c.154G>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_178311.3(GGTLC1):​c.154G>C​(p.Ala52Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000186 in 1,611,752 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A52S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00019 (5 hom.)
• Consequence: GGTLC1 NM_178311.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.58
• Publications: 4 publications found

Genes affected

GGTLC1 (HGNC:16437): (gamma-glutamyltransferase light chain 1) This gene encodes a member of the gamma-glutamyl transpeptidase (GGT) family, which are important in the metabolism of glutathione. The most ubiquitously expressed human GGT gene, GGT1, encodes a single transmembrane polypeptide that is post-translationally processed to form a heavy and a light chain. In contrast, the product of this gene only contains homology to the light chain region, and lacks a transmembrane domain. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Oct 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.076547444).
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGTLC1	NM_178311.3	c.154G>C	p.Ala52Pro	missense_variant	Exon 2 of 6	ENST00000335694.4	NP_842563.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGTLC1	ENST00000335694.4	c.154G>C	p.Ala52Pro	missense_variant	Exon 2 of 6	1	NM_178311.3	ENSP00000337587.4
GGTLC1	ENST00000278765.8	c.154G>C	p.Ala52Pro	missense_variant	Exon 2 of 6	1		ENSP00000278765.4
GGTLC1	ENST00000286890.8	c.154G>C	p.Ala52Pro	missense_variant	Exon 1 of 5	1		ENSP00000286890.4

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152178 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000353 AC: 88 AN: 249172 AF XY: 0.000451

Gnomad AFR exome AF: 0.0000631

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000980

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000188 AC: 275 AN: 1459456 Hom.: 5 Cov.: 44 AF XY: 0.000251 AC XY: 182 AN XY: 726056

African (AFR) AF: 0.00 AC: 0 AN: 33404

American (AMR) AF: 0.0000895 AC: 4 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00223 AC: 192 AN: 86140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53276

Middle Eastern (MID) AF: 0.000967 AC: 4 AN: 4136

European-Non Finnish (NFE) AF: 0.0000621 AC: 69 AN: 1111780

Other (OTH) AF: 0.0000997 AC: 6 AN: 60200

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152296 Hom.: 0 Cov.: 31 AF XY: 0.000175 AC XY: 13 AN XY: 74458

African (AFR) AF: 0.0000241 AC: 1 AN: 41562

American (AMR) AF: 0.000131 AC: 2 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000831

ExAC AF: 0.000420 AC: 51

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.073	T;T;T
Eigen	Benign	0.070
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.67	D
LIST_S2	Pathogenic	0.98	.;.;D
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.077	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.6	H;H;H
PhyloP100		5.6
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.4	D;D;D
REVEL	Benign	0.26
Sift	Uncertain	0.024	D;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.78
MVP		0.12
MPC		0.84
ClinPred		0.65	D
GERP RS		0.84
PromoterAI		-0.017	Neutral
Varity_R		0.81
gMVP		0.97
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs371694918; hg19: chr20-23967095;