chr7-30500641-C-T

Variant names:

• chr7-30500641-C-T
• rs758284260
• NM_024051.4:c.182G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024051.4(GGCT):​c.182G>A​(p.Ser61Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,613,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: GGCT NM_024051.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.05
• Publications: 8 publications found

Genes affected

GGCT (HGNC:21705): (gamma-glutamylcyclotransferase) The protein encoded by this gene catalyzes the formation of 5-oxoproline from gamma-glutamyl dipeptides, the penultimate step in glutathione catabolism, and may play a critical role in glutathione homeostasis. The encoded protein may also play a role in cell proliferation, and the expression of this gene is a potential marker for cancer. Pseudogenes of this gene are located on the long arm of chromosome 5 and the short arm of chromosomes 2 and 20. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

ENSG00000281039 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19350028).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024051.4. 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
	GGCT	NM_024051.4	MANE Select	c.182G>A	p.Ser61Asn	missense	Exon 2 of 4	NP_076956.1	O75223-1
	GGCT	NM_001199815.2		c.182G>A	p.Ser61Asn	missense	Exon 2 of 4	NP_001186744.1	O75223-4
	GGCT	NM_001199816.2		c.182G>A	p.Ser61Asn	missense	Exon 2 of 3	NP_001186745.1	O75223-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGCT	ENST00000275428.9	TSL:1 MANE Select	c.182G>A	p.Ser61Asn	missense	Exon 2 of 4	ENSP00000275428.4	O75223-1
	GGCT	ENST00000005374.10	TSL:1	c.182G>A	p.Ser61Asn	missense	Exon 2 of 3	ENSP00000005374.6	O75223-2
	ENSG00000281039	ENST00000598361.4	TSL:5	c.-74G>A		5_prime_UTR	Exon 3 of 5	ENSP00000470615.1	M0QZK8

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251320 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1461522 Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11 AN XY: 727046

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.000157 AC: 7 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111824

Other (OTH) AF: 0.0000331 AC: 2 AN: 60368

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152208 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74358

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.000196 AC: 3 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000386 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.000109

EpiControl AF: 0.00

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	Benign	0.33
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.069	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.0
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.15
Sift	Benign	0.34	T
Sift4G	Benign	0.21	T
Polyphen		0.16	B
Vest4		0.50
MVP		0.62
MPC		0.32
ClinPred		0.19	T
GERP RS		6.2
Varity_R		0.39
gMVP		0.80
Mutation Taster		=40/60	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs758284260; hg19: chr7-30540257;