rs12317459

Positions:

• chr12-82770777-G-A

Variant summary

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

The NM_152588.3(TMTC2):​c.83+83108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 151,926 control chromosomes in the GnomAD database, including 3,824 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 0.21 (3824 hom., cov: 31)
• Consequence: TMTC2 NM_152588.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

Genes affected

TMTC2 (HGNC:25440): (transmembrane O-mannosyltransferase targeting cadherins 2) The protein encoded by this gene is an integral membrane protein localized to the endoplasmic reticulum (ER). The encoded protein contains many tetratricopeptide repeats, sequences known for being involved in protein-protein interactions. This protein binds both the calcium uptake pump SERCA2B and the carbohydrate-binding chaperone calnexin, and it appears to play a role in calcium homeostasis in the ER. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMTC2	NM_152588.3	c.83+83108G>A		intron_variant		ENST00000321196.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMTC2	ENST00000321196.8	c.83+83108G>A		intron_variant		1	NM_152588.3	P1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32317 AN: 151808 Hom.: 3811 Cov.: 31

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.213 AC: 32359 AN: 151926 Hom.: 3824 Cov.: 31 AF XY: 0.209 AC XY: 15533 AN XY: 74242

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.204

Alfa AF: 0.192 Hom.: 4046

Bravo AF: 0.213

Asia WGS AF: 0.0810 AC: 282 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	0.15
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12317459; hg19: chr12-83164556;