Variant 22-27982363-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP2BP4_StrongBP6_Very_Strong

The NM_001145418.2(TTC28):c.7304G>A(p.Arg2435His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00408 in 1,540,914 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0043 ( 26 hom. )

Consequence

TTC28
NM_001145418.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0850

Variant links:

Genes affected

TTC28 (HGNC:29179): (tetratricopeptide repeat domain 28) Enables kinase binding activity. Involved in regulation of mitotic cell cycle. Located in midbody. [provided by Alliance of Genome Resources, Apr 2022]

TTC28 links:

TTC28-AS1 (HGNC:29336): (TTC28 antisense RNA 1)

TTC28-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PP2

Missense variant where missense usually causes diseases, TTC28

BP4

Computational evidence support a benign effect (MetaRNN=0.0032589138).

BP6

Variant 22-27982363-C-T is Benign according to our data. Variant chr22-27982363-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 778199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC28	NM_001145418.2 linkuse as main transcript	c.7304G>A	p.Arg2435His	missense_variant	23/23	ENST00000397906.7
TTC28-AS1	NR_026963.1 linkuse as main transcript	n.251-12110C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC28	ENST00000397906.7 linkuse as main transcript	c.7304G>A	p.Arg2435His	missense_variant	23/23	1	NM_001145418.2	P1
TTC28-AS1	ENST00000454741.5 linkuse as main transcript	n.206-12110C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00239

AC:

358

AN:

150104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000883

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.00119

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000215

Gnomad FIN

AF:

0.000478

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00398

Gnomad OTH

AF:

0.00293

GnomAD3 exomes

AF:

0.00199

AC:

304

AN:

152458

Hom.:

AF XY:

0.00202

AC XY:

163

AN XY:

80872

show subpopulations

Gnomad AFR exome

AF:

0.000511

Gnomad AMR exome

AF:

0.00108

Gnomad ASJ exome

AF:

0.000484

Gnomad EAS exome

AF:

0.000849

Gnomad SAS exome

AF:

0.000134

Gnomad FIN exome

AF:

0.000242

Gnomad NFE exome

AF:

0.00412

Gnomad OTH exome

AF:

0.00306

GnomAD4 exome

AF:

0.00426

AC:

5925

AN:

1390694

Hom.:

Cov.:

AF XY:

0.00411

AC XY:

2819

AN XY:

685878

show subpopulations

Gnomad4 AFR exome

AF:

0.000255

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.000322

Gnomad4 EAS exome

AF:

0.000200

Gnomad4 SAS exome

AF:

0.000166

Gnomad4 FIN exome

AF:

0.000450

Gnomad4 NFE exome

AF:

0.00516

Gnomad4 OTH exome

AF:

0.00472

GnomAD4 genome

AF:

0.00238

AC:

358

AN:

150220

Hom.:

Cov.:

AF XY:

0.00221

AC XY:

162

AN XY:

73282

show subpopulations

Gnomad4 AFR

AF:

0.000880

Gnomad4 AMR

AF:

0.00119

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000215

Gnomad4 FIN

AF:

0.000478

Gnomad4 NFE

AF:

0.00398

Gnomad4 OTH

AF:

0.00290

Alfa

AF:

0.00347

Hom.:

Bravo

AF:

0.00254

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00471

AC:

ExAC

AF:

0.00139

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

TTC28-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 01, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

Cadd

Benign

Dann

Benign

0.96

DEOGEN2

Benign

0.010

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.0033

T;T

MetaSVM

Benign

-0.66

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

Sift4G

Benign

0.14

T;T

Polyphen

0.0010

.;B

Vest4

0.069

MVP

0.095

ClinPred

0.16

GERP RS

1.6

Varity_R

0.030

gMVP

0.099

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

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