5-140627426-T-C

Variant names:

• chr5-140627426-T-C
• rs778588
• XM_011537665.3:c.-129-14239T>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.-129-14239T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,104 control chromosomes in the GnomAD database, including 8,547 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 0.33 (8547 hom., cov: 32)
• Consequence: TMCO6 XM_011537665.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137
• Publications: 10 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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 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: 0.325 AC: 49406 AN: 151986 Hom.: 8540 Cov.: 32

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.325 AC: 49451 AN: 152104 Hom.: 8547 Cov.: 32 AF XY: 0.326 AC XY: 24275 AN XY: 74358

African (AFR) AF: 0.428 AC: 17734 AN: 41472

American (AMR) AF: 0.298 AC: 4561 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1127 AN: 3464

East Asian (EAS) AF: 0.146 AC: 756 AN: 5188

South Asian (SAS) AF: 0.210 AC: 1016 AN: 4830

European-Finnish (FIN) AF: 0.337 AC: 3566 AN: 10570

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19808 AN: 67992

Other (OTH) AF: 0.315 AC: 662 AN: 2102

Alfa AF: 0.310 Hom.: 1784

Bravo AF: 0.325

Asia WGS AF: 0.199 AC: 692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.6
DANN	Benign	0.93
PhyloP100		0.14

Splicing

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

Other links and lift over

dbSNP: rs778588; hg19: chr5-140007011;