chr22-22646353-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199127.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGTLC2	NM_199127.3	MANE Select	c.8C>T	p.Ser3Phe	missense	Exon 2 of 6	NP_954578.2	Q14390
	GGTLC2	NM_001282879.2		c.8C>T	p.Ser3Phe	missense	Exon 2 of 5	NP_001269808.1	A0A494C1J8
	GGTLC2	NM_001391910.1		c.8C>T	p.Ser3Phe	missense	Exon 2 of 5	NP_001378839.1	A0A494C1J8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGTLC2	ENST00000448514.3	TSL:1 MANE Select	c.8C>T	p.Ser3Phe	missense	Exon 2 of 6	ENSP00000415676.2	Q14390
	GGTLC2	ENST00000480559.6	TSL:1	c.8C>T	p.Ser3Phe	missense	Exon 2 of 6	ENSP00000419751.1	Q14390
	GGTLC2	ENST00000417145.2	TSL:2	c.8C>T	p.Ser3Phe	missense	Exon 1 of 4	ENSP00000499086.1	A0A494C1J8

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD2 exomes AF: 0.0000144 AC: 3 AN: 208550 AF XY: 0.00000881

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31648

American (AMR) AF: 0.0000800 AC: 3 AN: 37492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23544

East Asian (EAS) AF: 0.00 AC: 0 AN: 33488

South Asian (SAS) AF: 0.00 AC: 0 AN: 83186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48038

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3782

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1024020

Other (OTH) AF: 0.00 AC: 0 AN: 54340

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00400497), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 19

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0090	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.96	T
MutationAssessor	Pathogenic	4.3	H
PhyloP100		5.1
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.49
MutPred		0.65		Loss of disorder (P = 0.0152)
MVP		0.37
MPC		1.2
ClinPred		0.70	D
PromoterAI		0.029	Neutral
Varity_R		0.66
gMVP		0.80
Mutation Taster		=56/44	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: rs1327092648; hg19: chr22-22988823;