rs2569192

Variant names:

• chr5-140635623-G-C
• rs2569192
• XM_011537665.3:c.-129-6042G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

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

African (AFR) AF: 0.247 AC: 10228 AN: 41490

American (AMR) AF: 0.268 AC: 4100 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1104 AN: 3472

East Asian (EAS) AF: 0.143 AC: 740 AN: 5162

South Asian (SAS) AF: 0.206 AC: 991 AN: 4822

European-Finnish (FIN) AF: 0.317 AC: 3346 AN: 10568

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.282 AC: 19141 AN: 67984

Other (OTH) AF: 0.261 AC: 551 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.59
PhyloP100		-0.23

Splicing

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

Other links and lift over

dbSNP: rs2569192; hg19: chr5-140015208;