Variant 22-27982324-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong

The NM_001145418.2(TTC28):c.7343C>T(p.Ala2448Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000739 in 1,529,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

TTC28
NM_001145418.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04

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 Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, TTC28

BP4

Computational evidence support a benign effect (MetaRNN=0.009000421).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC28	NM_001145418.2 linkuse as main transcript	c.7343C>T	p.Ala2448Val	missense_variant	23/23	ENST00000397906.7
TTC28-AS1	NR_026963.1 linkuse as main transcript	n.251-12149G>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.7343C>T	p.Ala2448Val	missense_variant	23/23	1	NM_001145418.2	P1
TTC28-AS1	ENST00000454741.5 linkuse as main transcript	n.206-12149G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000175

AC:

AN:

136954

Hom.:

AF XY:

0.000153

AC XY:

AN XY:

71964

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000262

Gnomad ASJ exome

AF:

0.00237

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000587

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000726

AC:

100

AN:

1377264

Hom.:

Cov.:

AF XY:

0.0000709

AC XY:

AN XY:

677152

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000415

Gnomad4 ASJ exome

AF:

0.00229

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.000175

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000347

Hom.:

Bravo

AF:

0.000136

ExAC

AF:

0.000132

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.7343C>T (p.A2448V) 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 7343, causing the alanine (A) at amino acid position 2448 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.37

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.017

T;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.47

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.067

MetaRNN

Benign

0.0090

T;T

MetaSVM

Benign

-0.57

MutationTaster

Benign

1.0

PrimateAI

Benign

0.48

Sift4G

Benign

0.15

T;T

Polyphen

0.019

.;B

Vest4

0.083

MVP

0.25

ClinPred

0.029

GERP RS

1.3

Varity_R

0.034

gMVP

0.13

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