rs778584

Variant names:

• chr5-140625627-T-C
• rs778584
• XM_011537665.3:c.-129-16038T>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.-129-16038T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 152,052 control chromosomes in the GnomAD database, including 25,095 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 0.57 (25095 hom., cov: 33)
• Consequence: TMCO6 XM_011537665.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 26 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 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: 0.566 AC: 85998 AN: 151934 Hom.: 25049 Cov.: 33

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.566 AC: 86102 AN: 152052 Hom.: 25095 Cov.: 33 AF XY: 0.568 AC XY: 42207 AN XY: 74324

African (AFR) AF: 0.690 AC: 28601 AN: 41474

American (AMR) AF: 0.525 AC: 8026 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1834 AN: 3470

East Asian (EAS) AF: 0.416 AC: 2149 AN: 5170

South Asian (SAS) AF: 0.466 AC: 2248 AN: 4824

European-Finnish (FIN) AF: 0.618 AC: 6520 AN: 10548

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35262 AN: 67966

Other (OTH) AF: 0.545 AC: 1150 AN: 2112

Alfa AF: 0.527 Hom.: 10261

Bravo AF: 0.560

Asia WGS AF: 0.513 AC: 1783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.59
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs778584; hg19: chr5-140005212;