Variant rs2303380 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017868.4(TTC12):c.504+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,605,108 control chromosomes in the GnomAD database, including 317,243 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 30800 hom., cov: 32)

Exomes 𝑓: 0.63 ( 286443 hom. )

Consequence

TTC12
NM_017868.4 splice_region, intron

Scores

Splicing: ADA: 0.00003587

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.506

Variant links:

Genes affected

TTC12 (HGNC:23700): (tetratricopeptide repeat domain 12) Involved in axonemal dynein complex assembly and sperm axoneme assembly. Located in centrosome and cytoplasm. Implicated in primary ciliary dyskinesia 45. [provided by Alliance of Genome Resources, Apr 2022]

TTC12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-113329987-G-A is Benign according to our data. Variant chr11-113329987-G-A is described in ClinVar as [Benign]. Clinvar id is 1287032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC12	NM_017868.4 linkuse as main transcript	c.504+8G>A		splice_region_variant, intron_variant		ENST00000529221.6	NP_060338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC12	ENST00000529221.6 linkuse as main transcript	c.504+8G>A		splice_region_variant, intron_variant		2	NM_017868.4	ENSP00000433757	A2	Q9H892-1

Frequencies

GnomAD3 genomes

AF:

0.634

AC:

96352

AN:

151940

Hom.:

30786

Cov.:

show subpopulations

Gnomad AFR

AF:

0.677

Gnomad AMI

AF:

0.660

Gnomad AMR

AF:

0.534

Gnomad ASJ

AF:

0.646

Gnomad EAS

AF:

0.541

Gnomad SAS

AF:

0.589

Gnomad FIN

AF:

0.678

Gnomad MID

AF:

0.640

Gnomad NFE

AF:

0.633

Gnomad OTH

AF:

0.643

GnomAD3 exomes

AF:

0.605

AC:

152147

AN:

251344

Hom.:

46941

AF XY:

0.611

AC XY:

82955

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.679

Gnomad AMR exome

AF:

0.452

Gnomad ASJ exome

AF:

0.657

Gnomad EAS exome

AF:

0.529

Gnomad SAS exome

AF:

0.597

Gnomad FIN exome

AF:

0.685

Gnomad NFE exome

AF:

0.635

Gnomad OTH exome

AF:

0.624

GnomAD4 exome

AF:

0.626

AC:

908914

AN:

1453048

Hom.:

286443

Cov.:

AF XY:

0.626

AC XY:

452668

AN XY:

723382

show subpopulations

Gnomad4 AFR exome

AF:

0.681

Gnomad4 AMR exome

AF:

0.469

Gnomad4 ASJ exome

AF:

0.666

Gnomad4 EAS exome

AF:

0.570

Gnomad4 SAS exome

AF:

0.604

Gnomad4 FIN exome

AF:

0.684

Gnomad4 NFE exome

AF:

0.630

Gnomad4 OTH exome

AF:

0.633

GnomAD4 genome

AF:

0.634

AC:

96414

AN:

152060

Hom.:

30800

Cov.:

AF XY:

0.633

AC XY:

47051

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.677

Gnomad4 AMR

AF:

0.533

Gnomad4 ASJ

AF:

0.646

Gnomad4 EAS

AF:

0.541

Gnomad4 SAS

AF:

0.588

Gnomad4 FIN

AF:

0.678

Gnomad4 NFE

AF:

0.633

Gnomad4 OTH

AF:

0.639

Alfa

AF:

0.631

Hom.:

40718

Bravo

AF:

0.624

Asia WGS

AF:

0.544

AC:

1893

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	- -

Ciliary dyskinesia, primary, 45

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.8

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000036

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over