chr5-140635910-G-A

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.

Variant Effect in Transcripts

 

RefSeq Transcripts

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

Ensembl Transcripts

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

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 v4.9

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;