rs3138078

Positions:

• chr5-140634532-C-A
• chr5-140634532-C-G
• chr5-140634532-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_011537665.3(TMCO6):​c.-129-7133C>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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMCO6	XM_011537665.3	c.-129-7133C>A		intron_variant			XP_011535967.1
TMCO6	XM_047417355.1	c.-242-5207C>A		intron_variant			XP_047273311.1
TMCO6	XM_047417356.1	c.-255-5207C>A		intron_variant			XP_047273312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

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

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.243

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 v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3138078; hg19: chr5-140014117;