22-22646353-C-T

Variant names:

• chr22-22646353-C-T
• rs1327092648
• NM_199127.3:c.8C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_199127.3(GGTLC2):​c.8C>T​(p.Ser3Phe) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0000022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GGTLC2 NM_199127.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.08

Genes affected

GGTLC2 (HGNC:18596): (gamma-glutamyltransferase light chain 2) This gene encodes a protein related to enzymes that cleaves gamma-glutamyl peptide bonds in glutathione and other peptides. Unlike similar proteins, the encoded protein contains only the light chain portion and may not have catalytic activity. Alternative splicing results in multiple transcript variants. There are several related family members and related pseudogene for this gene situated in the same region of chromosome 22. [provided by RefSeq, Sep 2013]

IGL (HGNC:5853):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGTLC2	NM_199127.3	c.8C>T	p.Ser3Phe	missense_variant	Exon 2 of 6	ENST00000448514.3	NP_954578.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGTLC2	ENST00000448514.3	c.8C>T	p.Ser3Phe	missense_variant	Exon 2 of 6	1	NM_199127.3	ENSP00000415676.2

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD3 exomes AF: 0.0000144 AC: 3 AN: 208550 Hom.: 0 AF XY: 0.00000881 AC XY: 1 AN XY: 113446

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000224 AC: 3 AN: 1339538 Hom.: 0 Cov.: 35 AF XY: 0.00000150 AC XY: 1 AN XY: 666642

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000800

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 19

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 26, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.8C>T (p.S3F) alteration is located in exon 1 (coding exon 1) of the GGTLC2 gene. This alteration results from a C to T substitution at nucleotide position 8, causing the serine (S) at amino acid position 3 to be replaced by a phenylalanine (F). 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	Pathogenic	0.70
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	.;.;T;.
Eigen	Benign	0.065
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.91	.;D;D;.
M_CAP	Benign	0.0090	T
MetaRNN	Uncertain	0.55	D;D;D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Pathogenic	4.3	.;.;H;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-5.3	.;.;D;D
REVEL	Benign	0.20
Sift	Pathogenic	0.0	.;.;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		1.0	.;.;D;.
Vest4		0.49
MutPred		0.65		Loss of disorder (P = 0.0152);Loss of disorder (P = 0.0152);Loss of disorder (P = 0.0152);Loss of disorder (P = 0.0152);
MVP		0.37
MPC		1.2
ClinPred		0.70	D
Varity_R		0.66
gMVP		0.80

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

LitVar

Other links and lift over

dbSNP: rs1327092648; hg19: chr22-22988823;