rs2260722

Positions:

• chr13-113533976-A-G
• chr13-113533976-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017905.6(TMCO3):​c.1344-69A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,217,590 control chromosomes in the GnomAD database, including 63,354 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 0.40 (13815 hom., cov: 33)
  • Exomes 𝑓: 0.29 (49539 hom.)
• Consequence: TMCO3 NM_017905.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

Genes affected

TMCO3 (HGNC:20329): (transmembrane and coiled-coil domains 3) This gene encodes a member of the monovalent cation:proton antiporter 2 (CPA2) family of transporter proteins. Members of this family typically couple the export of monovalent cations, such as potassium or sodium, to the import of protons across cellular membranes. Mutations in this gene have been identified in patients with a rare inherited vision defect, cornea guttata with anterior polar cataract. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMCO3	NM_017905.6	c.1344-69A>G		intron_variant		ENST00000434316.7	NP_060375.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMCO3	ENST00000434316.7	c.1344-69A>G		intron_variant		1	NM_017905.6	ENSP00000389399	P1
TMCO3	ENST00000375391.5	c.1226-15658A>G		intron_variant		1		ENSP00000364540
TMCO3	ENST00000474393.5	c.1344-69A>G		intron_variant		2		ENSP00000484053
TMCO3	ENST00000465556.1	n.189-5381A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.395 AC: 60111 AN: 152028 Hom.: 13799 Cov.: 33

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.388

GnomAD4 exome AF: 0.294 AC: 313454 AN: 1065444 Hom.: 49539 AF XY: 0.292 AC XY: 157369 AN XY: 538024

Gnomad4 AFR exome AF: 0.652

Gnomad4 AMR exome AF: 0.536

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.294

Gnomad4 SAS exome AF: 0.320

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.313

GnomAD4 genome AF: 0.396 AC: 60175 AN: 152146 Hom.: 13815 Cov.: 33 AF XY: 0.391 AC XY: 29121 AN XY: 74388

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.388

Alfa AF: 0.293 Hom.: 11419

Bravo AF: 0.424

Asia WGS AF: 0.350 AC: 1219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.2
DANN	Benign	0.60

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

Other links and lift over

dbSNP: rs2260722; hg19: chr13-114188291; COSMIC: COSV64807153; COSMIC: COSV64807153;