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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMCO6	XM_011537665.3	c.-129-14239T>C		intron_variant	Intron 1 of 10		XP_011535967.1
TMCO6	XM_047417355.1	c.-242-12313T>C		intron_variant	Intron 1 of 11		XP_047273311.1
TMCO6	XM_047417356.1	c.-255-12313T>C		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: 0.325 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 v4.3

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;