Variant 14-37749343-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001310135.5(TTC6):c.2768G>T(p.Arg923Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00119 in 1,491,800 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R923H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0011 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

TTC6
NM_001310135.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.80

Variant links:

Genes affected

TTC6 (HGNC:19739): (tetratricopeptide repeat domain 6)

TTC6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01342085).

BP6

Variant 14-37749343-G-T is Benign according to our data. Variant chr14-37749343-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3234156.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC6	NM_001310135.5 linkuse as main transcript	c.2768G>T	p.Arg923Leu	missense_variant	13/33	ENST00000553443.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC6	ENST00000553443.6 linkuse as main transcript	c.2768G>T	p.Arg923Leu	missense_variant	13/33	5	NM_001310135.5	P1
TTC6	ENST00000533625.5 linkuse as main transcript	c.*1062+10188G>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00110

AC:

168

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00128

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00191

AC:

205

AN:

107608

Hom.:

AF XY:

0.00196

AC XY:

115

AN XY:

58560

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00226

Gnomad ASJ exome

AF:

0.0113

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000312

Gnomad FIN exome

AF:

0.00164

Gnomad NFE exome

AF:

0.00148

Gnomad OTH exome

AF:

0.00415

GnomAD4 exome

AF:

0.00120

AC:

1607

AN:

1339538

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

833

AN XY:

655562

show subpopulations

Gnomad4 AFR exome

AF:

0.0000335

Gnomad4 AMR exome

AF:

0.00200

Gnomad4 ASJ exome

AF:

0.0117

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.00109

Gnomad4 NFE exome

AF:

0.00105

Gnomad4 OTH exome

AF:

0.00179

GnomAD4 genome

AF:

0.00110

AC:

168

AN:

152262

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000944

Gnomad4 NFE

AF:

0.00128

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00130

Hom.:

Bravo

AF:

0.00112

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00130

AC:

ExAC

AF:

0.00132

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

TTC6: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.55

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.62

M_CAP

Benign

0.066

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.58

PROVEAN

Pathogenic

-5.0

REVEL

Uncertain

0.29

Sift

Benign

0.044

Sift4G

Pathogenic

0.0

Vest4

0.62

MutPred

0.60

Gain of catalytic residue at I926 (P = 0);

MVP

0.68

MPC

0.26

ClinPred

0.11

GERP RS

5.8

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