rs370319355

Variant names:

Variant summary

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

The NM_001351059.2(TCIRG1):c.-1102C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000385 in 1,610,778 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

TCIRG1
NM_001351059.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 0.485

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive osteopetrosis
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Myriad Women’s Health, Orphanet
autosomal recessive osteopetrosis 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia
autosomal dominant severe congenital neutropenia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive osteopetrosis 6
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
dysosteosclerosis
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet

TCIRG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351059.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TCIRG1	NM_006019.4	MANE Select	c.148C>T	p.Arg50Cys	missense	Exon 3 of 20	NP_006010.2
TCIRG1	NM_001351059.2		c.-1102C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 19	NP_001337988.1
TCIRG1	NM_001440552.1		c.148C>T	p.Arg50Cys	missense	Exon 4 of 21	NP_001427481.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCIRG1	ENST00000265686.8	TSL:1 MANE Select	c.148C>T	p.Arg50Cys	missense	Exon 3 of 20	ENSP00000265686.3	Q13488-1
TCIRG1	ENST00000698255.1		c.148C>T	p.Arg50Cys	missense	Exon 3 of 20	ENSP00000513630.1	A0A8V8TM28
TCIRG1	ENST00000698254.1		c.148C>T	p.Arg50Cys	missense	Exon 3 of 16	ENSP00000513629.1	A0A8V8TN16

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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:

0.0000328

AC:

AN:

244216

AF XY:

0.0000302

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000552

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000295

AC:

AN:

1458530

Hom.:

Cov.:

AF XY:

0.0000317

AC XY:

AN XY:

725258

show subpopulations

African (AFR)

AF:

0.000509

AC:

AN:

33430

American (AMR)

AF:

0.0000225

AC:

AN:

44392

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26046

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39606

South Asian (SAS)

AF:

0.0000351

AC:

AN:

85470

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52834

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.0000171

AC:

AN:

1110734

Other (OTH)

AF:

0.0000166

AC:

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000125

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.000409

AC:

AN:

41534

American (AMR)

AF:

0.000131

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000986

Hom.:

Bravo

AF:

0.000106

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal recessive osteopetrosis 1 (1)

not provided (1)

TCIRG1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.79

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Benign

0.63

LIST_S2

Pathogenic

0.97

M_CAP

Uncertain

0.26

MetaRNN

Uncertain

0.67

MetaSVM

Uncertain

0.67

MutationAssessor

Uncertain

2.4

PhyloP100

0.48

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-4.5

REVEL

Pathogenic

0.82

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.28

MVP

0.95

MPC

0.77

ClinPred

0.89

GERP RS

3.7

Varity_R

0.58

gMVP

0.43

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over