11-68047512-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006019.4(TCIRG1):ā€‹c.1245G>Cā€‹(p.Leu415Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 1,614,050 control chromosomes in the GnomAD database, including 800,157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.98 ( 72930 hom., cov: 31)
Exomes š‘“: 1.0 ( 727227 hom. )

Consequence

TCIRG1
NM_006019.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.330
Variant links:
Genes affected
TCIRG1 (HGNC:11647): (T cell immune regulator 1, ATPase H+ transporting V0 subunit a3) This gene encodes a subunit of a large protein complex known as a vacuolar H+-ATPase (V-ATPase). The protein complex acts as a pump to move protons across the membrane. This movement of protons helps regulate the pH of cells and their surrounding environment. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, and receptor-mediated endocytosis. V-ATPase is comprised of a cytosolic V1 domain and a transmembrane V0 domain. Alternative splicing results in multiple transcript variants. Mutations in this gene are associated with infantile malignant osteopetrosis. [provided by RefSeq, May 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 11-68047512-G-C is Benign according to our data. Variant chr11-68047512-G-C is described in ClinVar as [Benign]. Clinvar id is 235632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-68047512-G-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.33 with no splicing effect.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TCIRG1NM_006019.4 linkuse as main transcriptc.1245G>C p.Leu415Leu synonymous_variant 11/20 ENST00000265686.8 NP_006010.2 Q13488-1A0A024R5E5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TCIRG1ENST00000265686.8 linkuse as main transcriptc.1245G>C p.Leu415Leu synonymous_variant 11/201 NM_006019.4 ENSP00000265686.3 Q13488-1

Frequencies

GnomAD3 genomes
AF:
0.978
AC:
148813
AN:
152142
Hom.:
72872
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.924
Gnomad AMI
AF:
1.00
Gnomad AMR
AF:
0.992
Gnomad ASJ
AF:
1.00
Gnomad EAS
AF:
1.00
Gnomad SAS
AF:
1.00
Gnomad FIN
AF:
1.00
Gnomad MID
AF:
0.981
Gnomad NFE
AF:
1.00
Gnomad OTH
AF:
0.986
GnomAD3 exomes
AF:
0.994
AC:
249461
AN:
250922
Hom.:
124057
AF XY:
0.996
AC XY:
135228
AN XY:
135806
show subpopulations
Gnomad AFR exome
AF:
0.923
Gnomad AMR exome
AF:
0.996
Gnomad ASJ exome
AF:
1.00
Gnomad EAS exome
AF:
1.00
Gnomad SAS exome
AF:
1.00
Gnomad FIN exome
AF:
1.00
Gnomad NFE exome
AF:
0.999
Gnomad OTH exome
AF:
0.996
GnomAD4 exome
AF:
0.997
AC:
1457975
AN:
1461790
Hom.:
727227
Cov.:
67
AF XY:
0.998
AC XY:
725561
AN XY:
727198
show subpopulations
Gnomad4 AFR exome
AF:
0.914
Gnomad4 AMR exome
AF:
0.996
Gnomad4 ASJ exome
AF:
1.00
Gnomad4 EAS exome
AF:
1.00
Gnomad4 SAS exome
AF:
1.00
Gnomad4 FIN exome
AF:
1.00
Gnomad4 NFE exome
AF:
1.00
Gnomad4 OTH exome
AF:
0.995
GnomAD4 genome
AF:
0.978
AC:
148929
AN:
152260
Hom.:
72930
Cov.:
31
AF XY:
0.979
AC XY:
72882
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.924
Gnomad4 AMR
AF:
0.992
Gnomad4 ASJ
AF:
1.00
Gnomad4 EAS
AF:
1.00
Gnomad4 SAS
AF:
1.00
Gnomad4 FIN
AF:
1.00
Gnomad4 NFE
AF:
1.00
Gnomad4 OTH
AF:
0.986
Alfa
AF:
0.952
Hom.:
21845
Bravo
AF:
0.975
Asia WGS
AF:
0.994
AC:
3457
AN:
3478
EpiCase
AF:
0.999
EpiControl
AF:
0.999

ClinVar

Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
Benign, criteria provided, single submitterclinical testingCenter for Pediatric Genomic Medicine, Children's Mercy Hospital and ClinicsJan 22, 2016- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not specified Benign:2
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Jan 24, 2017- -
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 29, 2016Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -
Autosomal recessive osteopetrosis 1 Benign:2
Benign, no assertion criteria providedclinical testingNatera, Inc.Sep 16, 2020- -
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 10, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
CADD
Benign
6.8
DANN
Benign
0.95
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs2471829; hg19: chr11-67814979; API