22-27983132-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2

The NM_001145418.2(TTC28):c.6535C>T(p.Arg2179Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00227 in 1,551,802 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 4 hom. )

Consequence

TTC28
NM_001145418.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 5.84

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 -8 ACMG points.

PP2

Missense variant where missense usually causes diseases, TTC28

BP4

Computational evidence support a benign effect (MetaRNN=0.011893421).

BP6

Variant 22-27983132-G-A is Benign according to our data. Variant chr22-27983132-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 774361.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS2

High Homozygotes in GnomAdExome at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC28	NM_001145418.2 linkuse as main transcript	c.6535C>T	p.Arg2179Cys	missense_variant	23/23	ENST00000397906.7
TTC28-AS1	NR_026963.1 linkuse as main transcript	n.251-11341G>A		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.6535C>T	p.Arg2179Cys	missense_variant	23/23	1	NM_001145418.2	P1
TTC28-AS1	ENST00000454741.5 linkuse as main transcript	n.206-11341G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00174

AC:

265

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00285

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00145

AC:

228

AN:

156834

Hom.:

AF XY:

0.00164

AC XY:

136

AN XY:

83088

show subpopulations

Gnomad AFR exome

AF:

0.000628

Gnomad AMR exome

AF:

0.000608

Gnomad ASJ exome

AF:

0.00177

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000878

Gnomad FIN exome

AF:

0.00130

Gnomad NFE exome

AF:

0.00242

Gnomad OTH exome

AF:

0.000908

GnomAD4 exome

AF:

0.00233

AC:

3260

AN:

1399496

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

1624

AN XY:

690252

show subpopulations

Gnomad4 AFR exome

AF:

0.000443

Gnomad4 AMR exome

AF:

0.000504

Gnomad4 ASJ exome

AF:

0.00143

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000846

Gnomad4 FIN exome

AF:

0.00199

Gnomad4 NFE exome

AF:

0.00270

Gnomad4 OTH exome

AF:

0.00200

GnomAD4 genome

AF:

0.00174

AC:

265

AN:

152306

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

123

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00285

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00252

Hom.:

Bravo

AF:

0.00156

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.00145

AC:

ESP6500EA

AF:

0.00314

AC:

ExAC

AF:

0.00172

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 30, 2021

The c.6535C>T (p.R2179C) alteration is located in exon 23 (coding exon 23) of the TTC28 gene. This alteration results from a C to T substitution at nucleotide position 6535, causing the arginine (R) at amino acid position 2179 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 03, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.090

Cadd

Uncertain

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.033

T;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

D;D

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.012

T;T

MetaSVM

Uncertain

0.44

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

Sift4G

Uncertain

0.013

D;D

Polyphen

1.0

.;D

Vest4

0.34

MVP

0.74

ClinPred

0.022

GERP RS

5.2

Varity_R

0.18

gMVP

0.25

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