12-88153205-A-G

Position:

• chr12-88153205-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_181783.4(TMTC3):​c.190-86A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 724,158 control chromosomes in the GnomAD database, including 131,188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (22281 hom., cov: 32)
  • Exomes 𝑓: 0.61 (108907 hom.)
• Consequence: TMTC3 NM_181783.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.06

Genes affected

TMTC3 (HGNC:26899): (transmembrane O-mannosyltransferase targeting cadherins 3) This gene encodes a protein that belongs to the transmembrane and tetratricopeptide repeat-containing protein family. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 12-88153205-A-G is Benign according to our data. Variant chr12-88153205-A-G is described in ClinVar as [Benign]. Clinvar id is 1250737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMTC3	NM_181783.4	c.190-86A>G		intron_variant		ENST00000266712.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMTC3	ENST00000266712.11	c.190-86A>G		intron_variant		1	NM_181783.4	P1
TMTC3	ENST00000547034.5	c.190-86A>G		intron_variant, NMD_transcript_variant		1
TMTC3	ENST00000549011.5	c.190-86A>G		intron_variant		4
TMTC3	ENST00000551088.1	c.190-1083A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77360 AN: 151864 Hom.: 22281 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.557

GnomAD4 exome AF: 0.611 AC: 349868 AN: 572178 Hom.: 108907 AF XY: 0.614 AC XY: 181275 AN XY: 295344

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.599

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.623

Gnomad4 SAS exome AF: 0.619

Gnomad4 FIN exome AF: 0.632

Gnomad4 NFE exome AF: 0.621

Gnomad4 OTH exome AF: 0.603

GnomAD4 genome AF: 0.509 AC: 77365 AN: 151980 Hom.: 22281 Cov.: 32 AF XY: 0.515 AC XY: 38234 AN XY: 74276

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.630

Gnomad4 FIN AF: 0.630

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.561

Alfa AF: 0.547 Hom.: 2931

Bravo AF: 0.493

Asia WGS AF: 0.596 AC: 2072 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.5
DANN	Benign	0.63

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: rs2468229; hg19: chr12-88546982;