rs2569193

Variant names:

• chr5-140635910-G-A
• rs2569193
• XM_011537665.3:c.-129-5755G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_011537665.3(TMCO6):​c.-129-5755G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,132 control chromosomes in the GnomAD database, including 5,522 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 (5522 hom., cov: 32)
• Consequence: TMCO6 XM_011537665.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0600
• Publications: 18 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=-0.76).
• 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.-129-5755G>A		intron_variant	Intron 1 of 10		XP_011535967.1
TMCO6	XM_047417355.1	c.-242-3829G>A		intron_variant	Intron 1 of 11		XP_047273311.1
TMCO6	XM_047417356.1	c.-255-3829G>A		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: 0.265 AC: 40318 AN: 152014 Hom.: 5524 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.265 AC: 40340 AN: 152132 Hom.: 5522 Cov.: 32 AF XY: 0.267 AC XY: 19892 AN XY: 74372

African (AFR) AF: 0.245 AC: 10169 AN: 41512

American (AMR) AF: 0.268 AC: 4094 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1104 AN: 3470

East Asian (EAS) AF: 0.144 AC: 742 AN: 5170

South Asian (SAS) AF: 0.205 AC: 987 AN: 4822

European-Finnish (FIN) AF: 0.316 AC: 3343 AN: 10576

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19138 AN: 67974

Other (OTH) AF: 0.260 AC: 550 AN: 2114

Alfa AF: 0.272 Hom.: 2968

Bravo AF: 0.258

Asia WGS AF: 0.184 AC: 637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.9
DANN	Benign	0.74
PhyloP100		0.060

Splicing

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

Other links and lift over

dbSNP: rs2569193; hg19: chr5-140015495;