Variant 22-27982396-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001145418.2(TTC28):c.7271C>G(p.Ala2424Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0428 in 1,551,410 control chromosomes in the GnomAD database, including 1,695 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.033 ( 112 hom., cov: 31)

Exomes 𝑓: 0.044 ( 1583 hom. )

Consequence

TTC28
NM_001145418.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.304

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021651983).

BP6

Variant 22-27982396-G-C is Benign according to our data. Variant chr22-27982396-G-C is described in ClinVar as [Benign]. Clinvar id is 3056496.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC28	NM_001145418.2 link	c.7271C>G	p.Ala2424Gly	missense_variant	23/23	ENST00000397906.7	NP_001138890.1	Q96AY4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC28	ENST00000397906.7 link	c.7271C>G	p.Ala2424Gly	missense_variant	23/23	1	NM_001145418.2	ENSP00000381003.2		Q96AY4

Frequencies

GnomAD3 genomes

AF:

0.0326

AC:

4964

AN:

152064

Hom.:

112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00828

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0340

Gnomad ASJ

AF:

0.0704

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00894

Gnomad FIN

AF:

0.0280

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0497

Gnomad OTH

AF:

0.0426

GnomAD3 exomes

AF:

0.0347

AC:

5415

AN:

156262

Hom.:

132

AF XY:

0.0340

AC XY:

2817

AN XY:

82824

show subpopulations

Gnomad AFR exome

AF:

0.00758

Gnomad AMR exome

AF:

0.0283

Gnomad ASJ exome

AF:

0.0753

Gnomad EAS exome

AF:

0.000183

Gnomad SAS exome

AF:

0.0115

Gnomad FIN exome

AF:

0.0295

Gnomad NFE exome

AF:

0.0507

Gnomad OTH exome

AF:

0.0452

GnomAD4 exome

AF:

0.0439

AC:

61405

AN:

1399228

Hom.:

1583

Cov.:

AF XY:

0.0429

AC XY:

29612

AN XY:

690128

show subpopulations

Gnomad4 AFR exome

AF:

0.00817

Gnomad4 AMR exome

AF:

0.0293

Gnomad4 ASJ exome

AF:

0.0738

Gnomad4 EAS exome

AF:

0.000112

Gnomad4 SAS exome

AF:

0.0106

Gnomad4 FIN exome

AF:

0.0298

Gnomad4 NFE exome

AF:

0.0492

Gnomad4 OTH exome

AF:

0.0423

GnomAD4 genome

AF:

0.0326

AC:

4964

AN:

152182

Hom.:

112

Cov.:

AF XY:

0.0306

AC XY:

2279

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00824

Gnomad4 AMR

AF:

0.0340

Gnomad4 ASJ

AF:

0.0704

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00936

Gnomad4 FIN

AF:

0.0280

Gnomad4 NFE

AF:

0.0497

Gnomad4 OTH

AF:

0.0422

Alfa

AF:

0.0469

Hom.:

150

Bravo

AF:

0.0340

TwinsUK

AF:

0.0558

AC:

207

ALSPAC

AF:

0.0475

AC:

183

ESP6500AA

AF:

0.00867

AC:

ESP6500EA

AF:

0.0603

AC:

192

ExAC

AF:

0.0267

AC:

709

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TTC28-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 03, 2020

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.079

DANN

Benign

0.62

DEOGEN2

Benign

0.013

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.55

T;T

MetaRNN

Benign

0.0022

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.90

.;L

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.32

.;N

REVEL

Benign

0.13

Sift

Benign

0.45

.;T

Sift4G

Benign

0.58

T;T

Polyphen

0.0

.;B

Vest4

0.024

ClinPred

0.0014

GERP RS

0.18

Varity_R

0.033

gMVP

0.068

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