5-140625525-C-T

Variant names:

• chr5-140625525-C-T
• rs778583
• XM_011537665.3:c.-129-16140C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_011537665.3(TMCO6):​c.-129-16140C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,082 control chromosomes in the GnomAD database, including 6,477 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 0.29 (6477 hom., cov: 32)
• Consequence: TMCO6 XM_011537665.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.665
• Publications: 15 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=-0.47).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.309 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: 0.287 AC: 43622 AN: 151964 Hom.: 6479 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.287 AC: 43652 AN: 152082 Hom.: 6477 Cov.: 32 AF XY: 0.288 AC XY: 21406 AN XY: 74334

African (AFR) AF: 0.314 AC: 13012 AN: 41484

American (AMR) AF: 0.275 AC: 4206 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1104 AN: 3464

East Asian (EAS) AF: 0.121 AC: 624 AN: 5176

South Asian (SAS) AF: 0.206 AC: 995 AN: 4826

European-Finnish (FIN) AF: 0.330 AC: 3482 AN: 10562

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19427 AN: 67972

Other (OTH) AF: 0.277 AC: 586 AN: 2112

Alfa AF: 0.283 Hom.: 22953

Bravo AF: 0.282

Asia WGS AF: 0.176 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	4.8
DANN	Benign	0.87
PhyloP100		0.67

Splicing

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

Other links and lift over

dbSNP: rs778583; hg19: chr5-140005110;