5-140634318-C-T

Variant names:

• chr5-140634318-C-T
• rs2569191
• XM_011537665.3:c.-129-7347C>T

Variant summary

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

The XM_011537665.3(TMCO6):​c.-129-7347C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 151,504 control chromosomes in the GnomAD database, including 24,302 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 0.56 (24302 hom., cov: 29)
• Consequence: TMCO6 XM_011537665.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 41 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMCO6	XM_011537665.3	c.-129-7347C>T		intron_variant	Intron 1 of 10		XP_011535967.1
TMCO6	XM_047417355.1	c.-242-5421C>T		intron_variant	Intron 1 of 11		XP_047273311.1
TMCO6	XM_047417356.1	c.-255-5421C>T		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: 0.561 AC: 84881 AN: 151392 Hom.: 24261 Cov.: 29

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.561 AC: 84973 AN: 151504 Hom.: 24302 Cov.: 29 AF XY: 0.564 AC XY: 41737 AN XY: 74008

African (AFR) AF: 0.655 AC: 27022 AN: 41260

American (AMR) AF: 0.528 AC: 8032 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1828 AN: 3466

East Asian (EAS) AF: 0.440 AC: 2260 AN: 5138

South Asian (SAS) AF: 0.467 AC: 2240 AN: 4796

European-Finnish (FIN) AF: 0.627 AC: 6543 AN: 10428

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.524 AC: 35596 AN: 67898

Other (OTH) AF: 0.545 AC: 1144 AN: 2100

Alfa AF: 0.553 Hom.: 3343

Bravo AF: 0.553

Asia WGS AF: 0.519 AC: 1805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.27
DANN	Benign	0.61
PhyloP100		-1.9

Splicing

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

Other links and lift over

dbSNP: rs2569191; hg19: chr5-140013903;