XM_011537665.3:c.-129-12831G>A

Variant names:

• chr5-140628834-G-A
• rs2569188
• XM_011537665.3:c.-129-12831G>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.-129-12831G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,942 control chromosomes in the GnomAD database, including 21,773 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 0.53 (21773 hom., cov: 32)
• Consequence: TMCO6 XM_011537665.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 20 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 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: 0.532 AC: 80786 AN: 151822 Hom.: 21743 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.532 AC: 80862 AN: 151942 Hom.: 21773 Cov.: 32 AF XY: 0.536 AC XY: 39781 AN XY: 74258

African (AFR) AF: 0.555 AC: 22992 AN: 41398

American (AMR) AF: 0.519 AC: 7936 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1831 AN: 3470

East Asian (EAS) AF: 0.444 AC: 2293 AN: 5166

South Asian (SAS) AF: 0.466 AC: 2247 AN: 4820

European-Finnish (FIN) AF: 0.623 AC: 6566 AN: 10534

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35592 AN: 67958

Other (OTH) AF: 0.519 AC: 1095 AN: 2108

Alfa AF: 0.518 Hom.: 10044

Bravo AF: 0.520

Asia WGS AF: 0.517 AC: 1797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.45
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs2569188; hg19: chr5-140008419; COSMIC: COSV57371340;