22-24586332-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_207644.3(LRRC75B):​c.502G>A​(p.Val168Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000644 in 1,613,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

LRRC75B
NM_207644.3 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0970
Variant links:
Genes affected
LRRC75B (HGNC:33155): (leucine rich repeat containing 75B) Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
GGT1 (HGNC:4250): (gamma-glutamyltransferase 1) The enzyme encoded by this gene is a type I gamma-glutamyltransferase that catalyzes the transfer of the glutamyl moiety of glutathione to a variety of amino acids and dipeptide acceptors. The enzyme is composed of a heavy chain and a light chain, which are derived from a single precursor protein. It is expressed in tissues involved in absorption and secretion and may contribute to the etiology of diabetes and other metabolic disorders. Multiple alternatively spliced variants have been identified. There are a number of related genes present on chromosomes 20 and 22, and putative pseudogenes for this gene on chromosomes 2, 13, and 22. [provided by RefSeq, Jan 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03428912).
BP6
Variant 22-24586332-C-T is Benign according to our data. Variant chr22-24586332-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2226320.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRRC75BNM_207644.3 linkc.502G>A p.Val168Met missense_variant Exon 4 of 4 ENST00000318753.13 NP_997527.2 Q2VPJ9-1
GGT1NM_013430.3 linkc.-429+2524C>T intron_variant Intron 1 of 15 NP_038347.2 P19440-1A0A140VJJ9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRRC75BENST00000318753.13 linkc.502G>A p.Val168Met missense_variant Exon 4 of 4 1 NM_207644.3 ENSP00000320520.8 Q2VPJ9-1
ENSG00000286070ENST00000652248.1 linkn.*167+2524C>T intron_variant Intron 5 of 19 ENSP00000499210.1

Frequencies

GnomAD3 genomes
AF:
0.0000525
AC:
8
AN:
152248
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000843
AC:
21
AN:
249010
Hom.:
0
AF XY:
0.0000962
AC XY:
13
AN XY:
135102
show subpopulations
Gnomad AFR exome
AF:
0.0000644
Gnomad AMR exome
AF:
0.000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000557
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000444
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000657
AC:
96
AN:
1461600
Hom.:
0
Cov.:
31
AF XY:
0.0000811
AC XY:
59
AN XY:
727124
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.0000188
Gnomad4 NFE exome
AF:
0.0000603
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152366
Hom.:
0
Cov.:
33
AF XY:
0.0000671
AC XY:
5
AN XY:
74510
show subpopulations
Gnomad4 AFR
AF:
0.0000240
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.0000579
Hom.:
0
Bravo
AF:
0.0000756
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000778
AC:
3
ExAC
AF:
0.0000495
AC:
6
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jun 09, 2022
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.083
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
0.41
DANN
Benign
0.78
DEOGEN2
Benign
0.0087
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.069
N
LIST_S2
Benign
0.58
T
M_CAP
Benign
0.0054
T
MetaRNN
Benign
0.034
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
L
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.26
N
REVEL
Benign
0.032
Sift
Benign
0.20
T
Sift4G
Benign
0.32
T
Polyphen
0.025
B
Vest4
0.11
MVP
0.19
MPC
0.16
ClinPred
0.016
T
GERP RS
-0.027
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.025
gMVP
0.20

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs774605663; hg19: chr22-24982300; COSMIC: COSV99959431; COSMIC: COSV99959431; API