Variant rs199973759 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_006019.4(TCIRG1):c.2285_2290dupTGGGCC(p.Leu762_Gly763dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.00361 in 1,613,774 control chromosomes in the GnomAD database, including 196 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 101 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 95 hom. )

Consequence

TCIRG1
NM_006019.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.46

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]

TCIRG1 links:

TCIRG1 (HGNC:):

TCIRG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_006019.4

BP6

Variant 11-68050524-A-AGGCCTG is Benign according to our data. Variant chr11-68050524-A-AGGCCTG is described in ClinVar as [Likely_benign]. Clinvar id is 305820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCIRG1	NM_006019.4 linkuse as main transcript	c.2285_2290dupTGGGCC	p.Leu762_Gly763dup	disruptive_inframe_insertion	19/20	ENST00000265686.8	NP_006010.2	Q13488-1A0A024R5E5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCIRG1	ENST00000265686.8 linkuse as main transcript	c.2285_2290dupTGGGCC	p.Leu762_Gly763dup	disruptive_inframe_insertion	19/20	1	NM_006019.4	ENSP00000265686.3		Q13488-1

Frequencies

GnomAD3 genomes

AF:

0.0194

AC:

2954

AN:

152188

Hom.:

101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0671

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00765

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.0186

GnomAD3 exomes

AF:

0.00509

AC:

1278

AN:

251248

Hom.:

AF XY:

0.00391

AC XY:

531

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.0688

Gnomad AMR exome

AF:

0.00333

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00196

AC:

2864

AN:

1461468

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

1222

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.0681

Gnomad4 AMR exome

AF:

0.00369

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000111

Gnomad4 OTH exome

AF:

0.00450

GnomAD4 genome

AF:

0.0194

AC:

2956

AN:

152306

Hom.:

101

Cov.:

AF XY:

0.0183

AC XY:

1364

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0670

Gnomad4 AMR

AF:

0.00764

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.0184

Alfa

AF:

0.00114

Hom.:

Bravo

AF:

0.0217

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 26, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Osteopetrosis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over