5-140625525-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMCO6	XM_011537665.3	c.-129-16140C>T		intron_variant	Intron 1 of 10		XP_011535967.1
TMCO6	XM_047417355.1	c.-242-14214C>T		intron_variant	Intron 1 of 11		XP_047273311.1
TMCO6	XM_047417356.1	c.-255-14214C>T		intron_variant	Intron 1 of 11		XP_047273312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

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

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.277

Alfa AF: 0.282 Hom.: 9438

Bravo AF: 0.282

Asia WGS AF: 0.176 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs778583; hg19: chr5-140005110;