5-140633982-T-G

Variant names:

• chr5-140633982-T-G
• rs5744454
• XM_011537665.3:c.-129-7683T>G

Variant summary

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

The XM_011537665.3(TMCO6):​c.-129-7683T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 151,624 control chromosomes in the GnomAD database, including 4,212 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 0.23 (4212 hom., cov: 30)
• Consequence: TMCO6 XM_011537665.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189

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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMCO6	XM_011537665.3	c.-129-7683T>G		intron_variant	Intron 1 of 10		XP_011535967.1
TMCO6	XM_047417355.1	c.-242-5757T>G		intron_variant	Intron 1 of 11		XP_047273311.1
TMCO6	XM_047417356.1	c.-255-5757T>G		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: 0.231 AC: 35055 AN: 151506 Hom.: 4197 Cov.: 30

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.231 AC: 35083 AN: 151624 Hom.: 4212 Cov.: 30 AF XY: 0.233 AC XY: 17280 AN XY: 74064

African (AFR) AF: 0.188 AC: 7774 AN: 41342

American (AMR) AF: 0.237 AC: 3612 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 727 AN: 3470

East Asian (EAS) AF: 0.295 AC: 1510 AN: 5126

South Asian (SAS) AF: 0.259 AC: 1241 AN: 4784

European-Finnish (FIN) AF: 0.307 AC: 3213 AN: 10476

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16418 AN: 67884

Other (OTH) AF: 0.236 AC: 496 AN: 2098

Alfa AF: 0.128 Hom.: 227

Bravo AF: 0.222

Asia WGS AF: 0.320 AC: 1112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.49
PhyloP100		-0.19
PromoterAI		0.039	Neutral

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

dbSNP: rs5744454; hg19: chr5-140013567;