22-24225572-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004121.5(GGT5):​c.1310G>A​(p.Arg437Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,612,662 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 11 hom., cov: 32)
Exomes 𝑓: 0.00068 ( 11 hom. )

Consequence

GGT5
NM_004121.5 missense

Scores

18

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.484
Variant links:
Genes affected
GGT5 (HGNC:4260): (gamma-glutamyltransferase 5) This gene is a member of the gamma-glutamyl transpeptidase gene family, and some reports indicate that it is capable of cleaving the gamma-glutamyl moiety of glutathione. The protein encoded by this gene is synthesized as a single, catalytically-inactive polypeptide, that is processed post-transcriptionally to form a heavy and light subunit, with the catalytic activity contained within the small subunit. The encoded enzyme is able to convert leukotriene C4 to leukotriene D4, but appears to have distinct substrate specificity compared to gamma-glutamyl transpeptidase. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0050580204).
BP6
Variant 22-24225572-C-T is Benign according to our data. Variant chr22-24225572-C-T is described in ClinVar as [Benign]. Clinvar id is 710165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00601 (915/152236) while in subpopulation AFR AF= 0.0211 (877/41546). AF 95% confidence interval is 0.02. There are 11 homozygotes in gnomad4. There are 420 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GGT5NM_004121.5 linkc.1310G>A p.Arg437Gln missense_variant Exon 9 of 12 ENST00000327365.10 NP_004112.2 P36269-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GGT5ENST00000327365.10 linkc.1310G>A p.Arg437Gln missense_variant Exon 9 of 12 1 NM_004121.5 ENSP00000330080.4 P36269-1
GGT5ENST00000398292.3 linkc.1310G>A p.Arg437Gln missense_variant Exon 9 of 12 1 ENSP00000381340.3 P36269-3
GGT5ENST00000263112.11 linkc.1214G>A p.Arg405Gln missense_variant Exon 8 of 11 1 ENSP00000263112.7 P36269-2
GGT5ENST00000425408.5 linkc.116G>A p.Arg39Gln missense_variant Exon 2 of 6 5 ENSP00000402917.1 H7C1X2

Frequencies

GnomAD3 genomes
AF:
0.00601
AC:
914
AN:
152118
Hom.:
11
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0211
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00164
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00288
GnomAD3 exomes
AF:
0.00155
AC:
388
AN:
250810
Hom.:
6
AF XY:
0.00122
AC XY:
166
AN XY:
135626
show subpopulations
Gnomad AFR exome
AF:
0.0207
Gnomad AMR exome
AF:
0.000839
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000150
Gnomad OTH exome
AF:
0.000654
GnomAD4 exome
AF:
0.000678
AC:
990
AN:
1460426
Hom.:
11
Cov.:
31
AF XY:
0.000637
AC XY:
463
AN XY:
726654
show subpopulations
Gnomad4 AFR exome
AF:
0.0215
Gnomad4 AMR exome
AF:
0.00107
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000128
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000109
Gnomad4 OTH exome
AF:
0.00139
GnomAD4 genome
AF:
0.00601
AC:
915
AN:
152236
Hom.:
11
Cov.:
32
AF XY:
0.00564
AC XY:
420
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.0211
Gnomad4 AMR
AF:
0.00163
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00285
Alfa
AF:
0.00261
Hom.:
2
Bravo
AF:
0.00680
ESP6500AA
AF:
0.0225
AC:
99
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.00189
AC:
229
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000296

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jan 30, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.076
BayesDel_addAF
Benign
-0.65
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
0.43
DANN
Benign
0.78
DEOGEN2
Benign
0.024
.;T;.
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.57
T;T;T
MetaRNN
Benign
0.0051
T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.34
.;N;N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.050
N;N;N
REVEL
Benign
0.022
Sift
Benign
0.70
T;T;T
Sift4G
Benign
0.63
T;T;T
Polyphen
0.0
B;B;.
Vest4
0.14
MVP
0.085
MPC
0.21
ClinPred
0.00070
T
GERP RS
-5.3
Varity_R
0.0080
gMVP
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs75273222; hg19: chr22-24621540; API