rs5744448

Variant names:

• chr5-140635324-G-T
• rs5744448
• XM_011537665.3:c.-129-6341G>T

Variant summary

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

The XM_011537665.3(TMCO6):​c.-129-6341G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.035 in 152,322 control chromosomes in the GnomAD database, including 237 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 0.035 (237 hom., cov: 33)
• Consequence: TMCO6 XM_011537665.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 3 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMCO6	XM_011537665.3	c.-129-6341G>T		intron_variant	Intron 1 of 10		XP_011535967.1
TMCO6	XM_047417355.1	c.-242-4415G>T		intron_variant	Intron 1 of 11		XP_047273311.1
TMCO6	XM_047417356.1	c.-255-4415G>T		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: 0.0350 AC: 5324 AN: 152204 Hom.: 236 Cov.: 33

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0222

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00733

Gnomad OTH AF: 0.0368

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

GnomAD4 genome AF: 0.0350 AC: 5330 AN: 152322 Hom.: 237 Cov.: 33 AF XY: 0.0336 AC XY: 2503 AN XY: 74486

African (AFR) AF: 0.105 AC: 4379 AN: 41550

American (AMR) AF: 0.0221 AC: 339 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4826

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10616

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00733 AC: 499 AN: 68038

Other (OTH) AF: 0.0364 AC: 77 AN: 2116

Alfa AF: 0.0296 Hom.: 24

Bravo AF: 0.0402

Asia WGS AF: 0.00664 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.5
DANN	Benign	0.79
PhyloP100		0.031

Splicing

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

Other links and lift over

dbSNP: rs5744448; hg19: chr5-140014909;