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GeneBe

22-27983070-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001145418.2(TTC28):c.6597G>A(p.Ala2199=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,551,658 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0018 ( 44 hom. )

Consequence

TTC28
NM_001145418.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.154
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-AS1 (HGNC:29336): (TTC28 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-27983070-C-T is Benign according to our data. Variant chr22-27983070-C-T is described in ClinVar as [Benign]. Clinvar id is 785920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.154 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00216 (329/152226) while in subpopulation EAS AF= 0.0333 (172/5164). AF 95% confidence interval is 0.0292. There are 3 homozygotes in gnomad4. There are 187 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TTC28NM_001145418.2 linkuse as main transcriptc.6597G>A p.Ala2199= synonymous_variant 23/23 ENST00000397906.7
TTC28-AS1NR_026963.1 linkuse as main transcriptn.251-11403C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TTC28ENST00000397906.7 linkuse as main transcriptc.6597G>A p.Ala2199= synonymous_variant 23/231 NM_001145418.2 P1
TTC28-AS1ENST00000454741.5 linkuse as main transcriptn.206-11403C>T intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00213
AC:
324
AN:
152108
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00687
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.0330
Gnomad SAS
AF:
0.00208
Gnomad FIN
AF:
0.000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000265
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00635
AC:
995
AN:
156588
Hom.:
19
AF XY:
0.00542
AC XY:
450
AN XY:
83002
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0226
Gnomad ASJ exome
AF:
0.00177
Gnomad EAS exome
AF:
0.0317
Gnomad SAS exome
AF:
0.000834
Gnomad FIN exome
AF:
0.00107
Gnomad NFE exome
AF:
0.000363
Gnomad OTH exome
AF:
0.00364
GnomAD4 exome
AF:
0.00179
AC:
2501
AN:
1399432
Hom.:
44
Cov.:
32
AF XY:
0.00174
AC XY:
1199
AN XY:
690226
show subpopulations
Gnomad4 AFR exome
AF:
0.0000316
Gnomad4 AMR exome
AF:
0.0194
Gnomad4 ASJ exome
AF:
0.00127
Gnomad4 EAS exome
AF:
0.0377
Gnomad4 SAS exome
AF:
0.00116
Gnomad4 FIN exome
AF:
0.00118
Gnomad4 NFE exome
AF:
0.000160
Gnomad4 OTH exome
AF:
0.00171
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00216
AC:
329
AN:
152226
Hom.:
3
Cov.:
32
AF XY:
0.00251
AC XY:
187
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.0000963
Gnomad4 AMR
AF:
0.00713
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.0333
Gnomad4 SAS
AF:
0.00208
Gnomad4 FIN
AF:
0.000943
Gnomad4 NFE
AF:
0.000265
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.000637
Hom.:
0
Bravo
AF:
0.00365
Asia WGS
AF:
0.0120
AC:
41
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

TTC28-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesAug 12, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.66
Cadd
Benign
5.2
Dann
Benign
0.76

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.

Other links and lift over

dbSNP: rs5762431; hg19: chr22-28379058; API