rs1682602

Positions:

• chr12-83012695-T-C

Variant summary

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

The ENST00000321196.8(TMTC2):​c.2071-18103T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,056 control chromosomes in the GnomAD database, including 47,691 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 0.78 (47691 hom., cov: 32)
• Consequence: TMTC2 ENST00000321196.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

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=-0.62).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMTC2	NM_152588.3	c.2071-18103T>C		intron_variant		ENST00000321196.8	NP_689801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMTC2	ENST00000321196.8	c.2071-18103T>C		intron_variant		1	NM_152588.3	ENSP00000322300	P1
TMTC2	ENST00000549919.1	c.2053-18103T>C		intron_variant		1		ENSP00000447609
TMTC2	ENST00000546590.2	c.*1392-18103T>C		intron_variant, NMD_transcript_variant		1		ENSP00000448630

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119048 AN: 151938 Hom.: 47677 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.928

Gnomad FIN AF: 0.893

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.811

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

GnomAD4 genome AF: 0.783 AC: 119103 AN: 152056 Hom.: 47691 Cov.: 32 AF XY: 0.791 AC XY: 58778 AN XY: 74310

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.842

Gnomad4 ASJ AF: 0.864

Gnomad4 EAS AF: 0.877

Gnomad4 SAS AF: 0.929

Gnomad4 FIN AF: 0.893

Gnomad4 NFE AF: 0.841

Gnomad4 OTH AF: 0.812

Alfa AF: 0.831 Hom.: 33397

Bravo AF: 0.769

Asia WGS AF: 0.868 AC: 3016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.9
DANN	Benign	0.87

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: rs1682602; hg19: chr12-83406474;