Variant chr20-23985310-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_178311.3(GGTLC1):c.584C>A(p.Thr195Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GGTLC1
NM_178311.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.207

Variant links:

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]

GGTLC1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05259353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GGTLC1	NM_178311.3 linkuse as main transcript	c.584C>A	p.Thr195Asn	missense_variant	6/6	ENST00000335694.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GGTLC1	ENST00000335694.4 linkuse as main transcript	c.584C>A	p.Thr195Asn	missense_variant	6/6	1	NM_178311.3	P1
GGTLC1	ENST00000278765.8 linkuse as main transcript	c.584C>A	p.Thr195Asn	missense_variant	6/6	1		P1
GGTLC1	ENST00000286890.8 linkuse as main transcript	c.584C>A	p.Thr195Asn	missense_variant	5/5	1		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459680

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726148

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.584C>A (p.T195N) alteration is located in exon 6 (coding exon 5) of the GGTLC1 gene. This alteration results from a C to A substitution at nucleotide position 584, causing the threonine (T) at amino acid position 195 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.0

DANN

Benign

0.53

DEOGEN2

Benign

0.0019

T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0010

M_CAP

Benign

0.0014

MetaRNN

Benign

0.053

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.16

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.16

N;N;N

REVEL

Benign

0.0080

Sift

Benign

0.49

T;T;T

Sift4G

Benign

0.47

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.091

MutPred

0.32

Loss of catalytic residue at T195 (P = 0.0724);Loss of catalytic residue at T195 (P = 0.0724);Loss of catalytic residue at T195 (P = 0.0724);

MVP

0.014

MPC

0.21

ClinPred

0.062

GERP RS

-1.7

Varity_R

0.046

gMVP

0.60

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over