rs2569188

Positions:

• chr5-140628834-G-A
• chr5-140628834-G-T

Variant summary

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

The XM_011537665.3(TMCO6):​c.-129-12831G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,942 control chromosomes in the GnomAD database, including 21,773 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 0.53 (21773 hom., cov: 32)
• Consequence: TMCO6 XM_011537665.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

Genes affected

TMCO6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMCO6	XM_011537665.3	c.-129-12831G>A		intron_variant			XP_011535967.1
TMCO6	XM_024446125.2	c.-472-10905G>A		intron_variant			XP_024301893.1
TMCO6	XM_047417355.1	c.-242-10905G>A		intron_variant			XP_047273311.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80786 AN: 151822 Hom.: 21743 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.532 AC: 80862 AN: 151942 Hom.: 21773 Cov.: 32 AF XY: 0.536 AC XY: 39781 AN XY: 74258

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.528

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.623

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.519

Alfa AF: 0.518 Hom.: 8921

Bravo AF: 0.520

Asia WGS AF: 0.517 AC: 1797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2569188; hg19: chr5-140008419; COSMIC: COSV57371340;