12-88148143-C-T

Position:

• chr12-88148143-C-T

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.-28-145C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 539,936 control chromosomes in the GnomAD database, including 239,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (65686 hom., cov: 31)
  • Exomes 𝑓: 0.95 (173852 hom.)
• Consequence: TMTC3 NM_181783.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.291

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=-0.95).
• BP6: Variant 12-88148143-C-T is Benign according to our data. Variant chr12-88148143-C-T is described in ClinVar as [Benign]. Clinvar id is 1288129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMTC3	NM_181783.4	c.-28-145C>T		intron_variant		ENST00000266712.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMTC3	ENST00000266712.11	c.-28-145C>T		intron_variant		1	NM_181783.4	P1
TMTC3	ENST00000547034.5	c.-28-145C>T		intron_variant, NMD_transcript_variant		1
TMTC3	ENST00000549011.5	c.-28-145C>T		intron_variant		4
TMTC3	ENST00000551088.1	c.-28-145C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.928 AC: 141183 AN: 152104 Hom.: 65651 Cov.: 31

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.953

Gnomad AMR AF: 0.938

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.906

Gnomad FIN AF: 0.988

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.948

Gnomad OTH AF: 0.933

GnomAD4 exome AF: 0.946 AC: 366959 AN: 387714 Hom.: 173852 AF XY: 0.944 AC XY: 191954 AN XY: 203398

Gnomad4 AFR exome AF: 0.876

Gnomad4 AMR exome AF: 0.951

Gnomad4 ASJ exome AF: 0.906

Gnomad4 EAS exome AF: 0.994

Gnomad4 SAS exome AF: 0.902

Gnomad4 FIN exome AF: 0.984

Gnomad4 NFE exome AF: 0.949

Gnomad4 OTH exome AF: 0.935

GnomAD4 genome AF: 0.928 AC: 141273 AN: 152222 Hom.: 65686 Cov.: 31 AF XY: 0.930 AC XY: 69257 AN XY: 74440

Gnomad4 AFR AF: 0.873

Gnomad4 AMR AF: 0.938

Gnomad4 ASJ AF: 0.897

Gnomad4 EAS AF: 0.990

Gnomad4 SAS AF: 0.907

Gnomad4 FIN AF: 0.988

Gnomad4 NFE AF: 0.948

Gnomad4 OTH AF: 0.934

Alfa AF: 0.938 Hom.: 13624

Bravo AF: 0.924

Asia WGS AF: 0.929 AC: 3229 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	-0.95
CADD	Benign	1.4
DANN	Benign	0.33

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: rs2468227; hg19: chr12-88541920;