XM_011537665.3:c.-129-4403G>A

Variant names:

• chr5-140637262-G-A
• rs5744441
• XM_011537665.3:c.-129-4403G>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.-129-4403G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,106 control chromosomes in the GnomAD database, including 3,471 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 0.20 (3471 hom., cov: 32)
• Consequence: TMCO6 XM_011537665.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.812
• Publications: 22 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMCO6	XM_011537665.3	c.-129-4403G>A		intron_variant	Intron 1 of 10		XP_011535967.1
TMCO6	XM_047417355.1	c.-242-2477G>A		intron_variant	Intron 1 of 11		XP_047273311.1
TMCO6	XM_047417356.1	c.-255-2477G>A		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: 0.196 AC: 29821 AN: 151988 Hom.: 3458 Cov.: 32

Gnomad AFR AF: 0.0829

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.196 AC: 29844 AN: 152106 Hom.: 3471 Cov.: 32 AF XY: 0.199 AC XY: 14828 AN XY: 74328

African (AFR) AF: 0.0827 AC: 3432 AN: 41518

American (AMR) AF: 0.215 AC: 3289 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 703 AN: 3470

East Asian (EAS) AF: 0.295 AC: 1526 AN: 5168

South Asian (SAS) AF: 0.253 AC: 1221 AN: 4818

European-Finnish (FIN) AF: 0.306 AC: 3226 AN: 10538

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15941 AN: 67990

Other (OTH) AF: 0.199 AC: 419 AN: 2106

Alfa AF: 0.188 Hom.: 1040

Bravo AF: 0.182

Asia WGS AF: 0.308 AC: 1072 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.62
PhyloP100		-0.81

Splicing

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

Other links and lift over

dbSNP: rs5744441; hg19: chr5-140016847;