XM_011537665.3:c.-129-7133C>A

Variant names:

• chr5-140634532-C-A
• rs3138078
• XM_011537665.3:c.-129-7133C>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.-129-7133C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 137,310 control chromosomes in the GnomAD database, including 3,871 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 0.24 (3871 hom., cov: 23)
• Consequence: TMCO6 XM_011537665.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437
• Publications: 11 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.29 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: 0.239 AC: 32755 AN: 137256 Hom.: 3861 Cov.: 23

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.0520

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.181

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.239 AC: 32764 AN: 137310 Hom.: 3871 Cov.: 23 AF XY: 0.242 AC XY: 15868 AN XY: 65574

African (AFR) AF: 0.200 AC: 7162 AN: 35800

American (AMR) AF: 0.266 AC: 3354 AN: 12620

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 720 AN: 3406

East Asian (EAS) AF: 0.303 AC: 1419 AN: 4682

South Asian (SAS) AF: 0.265 AC: 1153 AN: 4354

European-Finnish (FIN) AF: 0.325 AC: 2459 AN: 7558

Middle Eastern (MID) AF: 0.165 AC: 35 AN: 212

European-Non Finnish (NFE) AF: 0.242 AC: 15958 AN: 65896

Other (OTH) AF: 0.243 AC: 457 AN: 1878

Alfa AF: 0.222 Hom.: 471

Bravo AF: 0.221

Asia WGS AF: 0.317 AC: 1102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.7
DANN	Benign	0.67
PhyloP100		-0.44

Splicing

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

Other links and lift over

dbSNP: rs3138078; hg19: chr5-140014117;