rs7298326

Positions:

• chr12-83131459-A-G

Variant summary

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

The ENST00000321196.8(TMTC2):​c.2332-751A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,066 control chromosomes in the GnomAD database, including 6,999 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 0.29 (6999 hom., cov: 33)
• Consequence: TMTC2 ENST00000321196.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMTC2	NM_152588.3	c.2332-751A>G		intron_variant		ENST00000321196.8	NP_689801.1
TMTC2	NM_001320321.2	c.1597-751A>G		intron_variant			NP_001307250.1
TMTC2	XM_017018884.3	c.1981-751A>G		intron_variant			XP_016874373.1
TMTC2	XM_024448863.2	c.1981-751A>G		intron_variant			XP_024304631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMTC2	ENST00000321196.8	c.2332-751A>G		intron_variant		1	NM_152588.3	ENSP00000322300	P1
TMTC2	ENST00000549919.1	c.2314-751A>G		intron_variant		1		ENSP00000447609
TMTC2	ENST00000546590.2	c.*1653-751A>G		intron_variant, NMD_transcript_variant		1		ENSP00000448630

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44566 AN: 151946 Hom.: 6990 Cov.: 33

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.293 AC: 44609 AN: 152066 Hom.: 6999 Cov.: 33 AF XY: 0.290 AC XY: 21597 AN XY: 74350

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.276

Alfa AF: 0.280 Hom.: 831

Bravo AF: 0.292

Asia WGS AF: 0.324 AC: 1124 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	14
DANN	Benign	0.77

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: rs7298326; hg19: chr12-83525238;