11-68049783-C-G

Variant names:

• chr11-68049783-C-G
• NM_006019.4:c.2008C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006019.4(TCIRG1):​c.2008C>G​(p.Arg670Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000141 in 1,418,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: TCIRG1 NM_006019.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.654

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05510232).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCIRG1	NM_006019.4	c.2008C>G	p.Arg670Gly	missense_variant	Exon 16 of 20	ENST00000265686.8	NP_006010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCIRG1	ENST00000265686.8	c.2008C>G	p.Arg670Gly	missense_variant	Exon 16 of 20	1	NM_006019.4	ENSP00000265686.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000141 AC: 20 AN: 1418152 Hom.: 0 Cov.: 33 AF XY: 0.0000128 AC XY: 9 AN XY: 703022

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.8
DANN	Benign	0.42
DEOGEN2	Benign	0.22	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.32	T;T
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.055	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	-0.52	N;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.18	N;N
REVEL	Benign	0.14
Sift	Benign	0.56	T;T
Sift4G	Benign	0.46	T;T
Polyphen		0.0	B;.
Vest4		0.077
MutPred		0.43		Loss of solvent accessibility (P = 0.0146);.;
MVP		0.25
MPC		0.20
ClinPred		0.017	T
GERP RS		-3.2
Varity_R		0.053
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-67817250;