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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMCO6	XM_011537665.3	c.-129-6042G>C		intron_variant	Intron 1 of 10		XP_011535967.1
TMCO6	XM_047417355.1	c.-242-4116G>C		intron_variant	Intron 1 of 11		XP_047273311.1
TMCO6	XM_047417356.1	c.-255-4116G>C		intron_variant	Intron 1 of 11		XP_047273312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	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

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 v4.3

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;