chr5-140626201-T-C

Variant names:

• chr5-140626201-T-C
• rs7721577
• XM_011537665.3:c.-129-15464T>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.-129-15464T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 151,402 control chromosomes in the GnomAD database, including 3,425 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 (3425 hom., cov: 31)
• Consequence: TMCO6 XM_011537665.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40
• Publications: 19 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMCO6	XM_011537665.3	c.-129-15464T>C		intron_variant	Intron 1 of 10		XP_011535967.1
TMCO6	XM_047417355.1	c.-242-13538T>C		intron_variant	Intron 1 of 11		XP_047273311.1
TMCO6	XM_047417356.1	c.-255-13538T>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: 0.195 AC: 29552 AN: 151288 Hom.: 3413 Cov.: 31

Gnomad AFR AF: 0.0856

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.195 AC: 29575 AN: 151402 Hom.: 3425 Cov.: 31 AF XY: 0.197 AC XY: 14593 AN XY: 73926

African (AFR) AF: 0.0854 AC: 3516 AN: 41160

American (AMR) AF: 0.219 AC: 3328 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 708 AN: 3472

East Asian (EAS) AF: 0.298 AC: 1537 AN: 5164

South Asian (SAS) AF: 0.256 AC: 1234 AN: 4812

European-Finnish (FIN) AF: 0.285 AC: 2962 AN: 10404

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

European-Non Finnish (NFE) AF: 0.232 AC: 15777 AN: 67898

Other (OTH) AF: 0.202 AC: 426 AN: 2108

Alfa AF: 0.217 Hom.: 6230

Bravo AF: 0.183

Asia WGS AF: 0.318 AC: 1105 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	0.98
DANN	Benign	0.35
PhyloP100		-2.4

Splicing

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

Other links and lift over

dbSNP: rs7721577; hg19: chr5-140005786;