rs2569192

Positions:

• chr5-140635623-G-C

Variant summary

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

The XM_011537665.3(TMCO6):​c.-129-6042G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,104 control chromosomes in the GnomAD database, including 5,545 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 0.27 (5545 hom., cov: 32)
• Consequence: TMCO6 XM_011537665.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231

Genes affected

TMCO6 (HGNC:28814): (transmembrane and coiled-coil domains 6) Predicted to enable nuclear import signal receptor activity. Predicted to be involved in protein import into nucleus. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMCO6	XM_011537665.3	c.-129-6042G>C		intron_variant			XP_011535967.1
TMCO6	XM_047417355.1	c.-242-4116G>C		intron_variant			XP_047273311.1
TMCO6	XM_047417356.1	c.-255-4116G>C		intron_variant			XP_047273312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40392 AN: 151986 Hom.: 5547 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.263

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.266 AC: 40414 AN: 152104 Hom.: 5545 Cov.: 32 AF XY: 0.268 AC XY: 19933 AN XY: 74332

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.261

Alfa AF: 0.277 Hom.: 716

Bravo AF: 0.259

Asia WGS AF: 0.184 AC: 638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2569192; hg19: chr5-140015208;