chr12-83046851-C-T

Position:

• chr12-83046851-C-T

Variant summary

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

The NM_152588.3(TMTC2):​c.2153-4053C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0731 in 152,184 control chromosomes in the GnomAD database, including 465 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 0.073 (465 hom., cov: 33)
• Consequence: TMTC2 NM_152588.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.092 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMTC2	NM_152588.3	c.2153-4053C>T		intron_variant		ENST00000321196.8	NP_689801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMTC2	ENST00000321196.8	c.2153-4053C>T		intron_variant		1	NM_152588.3	ENSP00000322300.3
TMTC2	ENST00000549919.1	c.2135-4053C>T		intron_variant		1		ENSP00000447609.1
TMTC2	ENST00000546590.2	n.*1474-4053C>T		intron_variant		1		ENSP00000448630.2

Frequencies

GnomAD3 genomes AF: 0.0729 AC: 11090 AN: 152066 Hom.: 463 Cov.: 33

Gnomad AFR AF: 0.0940

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0553

Gnomad ASJ AF: 0.0541

Gnomad EAS AF: 0.0808

Gnomad SAS AF: 0.0495

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0607

Gnomad OTH AF: 0.0676

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

GnomAD4 genome AF: 0.0731 AC: 11118 AN: 152184 Hom.: 465 Cov.: 33 AF XY: 0.0736 AC XY: 5476 AN XY: 74400

Gnomad4 AFR AF: 0.0944

Gnomad4 AMR AF: 0.0552

Gnomad4 ASJ AF: 0.0541

Gnomad4 EAS AF: 0.0814

Gnomad4 SAS AF: 0.0495

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0608

Gnomad4 OTH AF: 0.0664

Alfa AF: 0.0623 Hom.: 463

Bravo AF: 0.0715

Asia WGS AF: 0.0720 AC: 249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.51
DANN	Benign	0.71

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: rs7304787; hg19: chr12-83440630;