Variant 14-20295444-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_138376.3(TTC5):c.926A>G(p.Tyr309Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0101 in 1,614,172 control chromosomes in the GnomAD database, including 120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0060 ( 7 hom., cov: 32)

Exomes 𝑓: 0.011 ( 113 hom. )

Consequence

TTC5
NM_138376.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.66

Variant links:

Genes affected

TTC5 (HGNC:19274): (tetratricopeptide repeat domain 5) Predicted to enable DNA binding activity and chromatin binding activity. Predicted to be involved in DNA repair. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TTC5 links:

TTC5 (HGNC:):

TTC5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066043437).

BP6

Variant 14-20295444-T-C is Benign according to our data. Variant chr14-20295444-T-C is described in ClinVar as [Benign]. Clinvar id is 2644041.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00597 (909/152294) while in subpopulation NFE AF= 0.0105 (712/68008). AF 95% confidence interval is 0.00983. There are 7 homozygotes in gnomad4. There are 404 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC5	NM_138376.3 linkuse as main transcript	c.926A>G	p.Tyr309Cys	missense_variant	8/10	ENST00000258821.8	NP_612385.2	Q8N0Z6Q86T04

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TTC5	ENST00000258821.8 linkuse as main transcript	c.926A>G	p.Tyr309Cys	missense_variant	8/10	1	NM_138376.3	ENSP00000258821.3	Q8N0Z6
TTC5	ENST00000383029.7 linkuse as main transcript	n.*471A>G		non_coding_transcript_exon_variant	8/10	1		ENSP00000372496.3	H9KV81
TTC5	ENST00000383029.7 linkuse as main transcript	n.*471A>G		3_prime_UTR_variant	8/10	1		ENSP00000372496.3	H9KV81
TTC5	ENST00000554157.5 linkuse as main transcript	n.937A>G		non_coding_transcript_exon_variant	8/9	2

Frequencies

GnomAD3 genomes

AF:

0.00598

AC:

910

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00571

AC:

1436

AN:

251350

Hom.:

AF XY:

0.00604

AC XY:

820

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00228

Gnomad AMR exome

AF:

0.00231

Gnomad ASJ exome

AF:

0.00437

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00193

Gnomad FIN exome

AF:

0.00254

Gnomad NFE exome

AF:

0.00987

Gnomad OTH exome

AF:

0.00636

GnomAD4 exome

AF:

0.0106

AC:

15426

AN:

1461878

Hom.:

113

Cov.:

AF XY:

0.0103

AC XY:

7504

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00161

Gnomad4 AMR exome

AF:

0.00275

Gnomad4 ASJ exome

AF:

0.00513

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00219

Gnomad4 FIN exome

AF:

0.00264

Gnomad4 NFE exome

AF:

0.0129

Gnomad4 OTH exome

AF:

0.00770

GnomAD4 genome

AF:

0.00597

AC:

909

AN:

152294

Hom.:

Cov.:

AF XY:

0.00542

AC XY:

404

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00183

Gnomad4 AMR

AF:

0.00359

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.0105

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00963

Hom.:

Bravo

AF:

0.00602

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0110

AC:

ExAC

AF:

0.00559

AC:

679

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0115

EpiControl

AF:

0.0111

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

TTC5: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.0066

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-5.1

REVEL

Benign

0.16

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.019

Polyphen

1.0

Vest4

0.54

MVP

0.49

MPC

0.71

ClinPred

0.035

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.55

gMVP

0.79

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