rs3138076

Positions:

• chr5-140635028-T-C
• chr5-140635028-T-G

Variant summary

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

The XM_011537665.3(TMCO6):​c.-129-6637T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 151,256 control chromosomes in the GnomAD database, including 4,240 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 0.23 (4240 hom., cov: 33)
• Consequence: TMCO6 XM_011537665.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.730

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMCO6	XM_011537665.3	c.-129-6637T>C		intron_variant			XP_011535967.1
TMCO6	XM_047417355.1	c.-242-4711T>C		intron_variant			XP_047273311.1
TMCO6	XM_047417356.1	c.-255-4711T>C		intron_variant			XP_047273312.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35174 AN: 151134 Hom.: 4225 Cov.: 33

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.0547

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.163

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.233 AC: 35202 AN: 151256 Hom.: 4240 Cov.: 33 AF XY: 0.235 AC XY: 17364 AN XY: 73918

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.239

Alfa AF: 0.234 Hom.: 503

Bravo AF: 0.223

Asia WGS AF: 0.319 AC: 1109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3138076; hg19: chr5-140014613;