rs3794186

Variant names:

• chr11-68053569-G-A
• rs3794186
• NM_001277.3:c.*419C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001277.3(CHKA):​c.*419C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0824 in 178,460 control chromosomes in the GnomAD database, including 695 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.084 (600 hom., cov: 32)
  • Exomes 𝑓: 0.071 (95 hom.)
• Consequence: CHKA NM_001277.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.854
• Publications: 22 publications found

Genes affected

CHKA (HGNC:1937): (choline kinase alpha) The major pathway for the biosynthesis of phosphatidylcholine occurs via the CDP-choline pathway. The protein encoded by this gene is the initial enzyme in the sequence and may play a regulatory role. The encoded protein also catalyzes the phosphorylation of ethanolamine. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000255031 (HGNC:):

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)
• 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: Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHKA	NM_001277.3	c.*419C>T		3_prime_UTR_variant	Exon 12 of 12	ENST00000265689.9	NP_001268.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHKA	ENST00000265689.9	c.*419C>T		3_prime_UTR_variant	Exon 12 of 12	1	NM_001277.3	ENSP00000265689.4

Frequencies

GnomAD3 genomes AF: 0.0844 AC: 12832 AN: 152004 Hom.: 596 Cov.: 32

Gnomad AFR AF: 0.0883

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0641

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.0615

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0753

Gnomad OTH AF: 0.0679

GnomAD4 exome AF: 0.0706 AC: 1860 AN: 26338 Hom.: 95 Cov.: 0 AF XY: 0.0679 AC XY: 967 AN XY: 14246

African (AFR) AF: 0.0503 AC: 31 AN: 616

American (AMR) AF: 0.0540 AC: 86 AN: 1594

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 24 AN: 570

East Asian (EAS) AF: 0.130 AC: 104 AN: 802

South Asian (SAS) AF: 0.0496 AC: 208 AN: 4196

European-Finnish (FIN) AF: 0.122 AC: 151 AN: 1242

Middle Eastern (MID) AF: 0.0238 AC: 2 AN: 84

European-Non Finnish (NFE) AF: 0.0730 AC: 1160 AN: 15890

Other (OTH) AF: 0.0699 AC: 94 AN: 1344

GnomAD4 genome AF: 0.0845 AC: 12850 AN: 152122 Hom.: 600 Cov.: 32 AF XY: 0.0875 AC XY: 6502 AN XY: 74350

African (AFR) AF: 0.0884 AC: 3666 AN: 41474

American (AMR) AF: 0.0641 AC: 980 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0533 AC: 185 AN: 3470

East Asian (EAS) AF: 0.168 AC: 870 AN: 5178

South Asian (SAS) AF: 0.0618 AC: 298 AN: 4824

European-Finnish (FIN) AF: 0.139 AC: 1466 AN: 10584

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0754 AC: 5124 AN: 67996

Other (OTH) AF: 0.0676 AC: 143 AN: 2114

Alfa AF: 0.0722 Hom.: 805

Bravo AF: 0.0764

Asia WGS AF: 0.122 AC: 421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.9
DANN	Benign	0.82
PhyloP100		0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3794186; hg19: chr11-67821036;