14-75902201-T-C

Position:

chr14-75902201-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015072.5(TTLL5):c.3800T>C(p.Phe1267Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,613,720 control chromosomes in the GnomAD database, including 50,283 homozygotes. 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 Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.31 ( 9156 hom., cov: 32)

Exomes 𝑓: 0.22 ( 41127 hom. )

Consequence

TTLL5
NM_015072.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.386

Variant links:

Genes affected

TTLL5 (HGNC:19963): (tubulin tyrosine ligase like 5) This gene encodes a member of the tubulin tyrosine ligase like protein family. This protein interacts with two glucocorticoid receptor coactivators, transcriptional intermediary factor 2 and steroid receptor coactivator 1. This protein may function as a coregulator of glucocorticoid receptor mediated gene induction and repression. This protein may also function as an alpha tubulin polyglutamylase.[provided by RefSeq, Feb 2010]

TTLL5 links:

IFT43 (HGNC:29669): (intraflagellar transport 43) This gene encodes a subunit of the intraflagellar transport complex A (IFT-A). IFT-A is a multiprotein complex that plays an important role in cilia assembly and maintenance by mediating retrograde ciliary transport. Mutations in this gene are a cause of cranioectodermal dysplasia-3 (CED3), also known as Sensenbrenner syndrome. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

IFT43 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.6160398E-5).

BP6

Variant 14-75902201-T-C is Benign according to our data. Variant chr14-75902201-T-C is described in ClinVar as [Benign]. Clinvar id is 677213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTLL5	NM_015072.5 linkuse as main transcript	c.3800T>C	p.Phe1267Ser	missense_variant	31/32	ENST00000298832.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTLL5	ENST00000298832.14 linkuse as main transcript	c.3800T>C	p.Phe1267Ser	missense_variant	31/32	1	NM_015072.5	P4	Q6EMB2-1

Frequencies

GnomAD3 genomes

AF:

0.309

AC:

46873

AN:

151924

Hom.:

9126

Cov.:

show subpopulations

Gnomad AFR

AF:

0.517

Gnomad AMI

AF:

0.424

Gnomad AMR

AF:

0.356

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.511

Gnomad SAS

AF:

0.411

Gnomad FIN

AF:

0.143

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.307

GnomAD3 exomes

AF:

0.282

AC:

70728

AN:

250988

Hom.:

12395

AF XY:

0.278

AC XY:

37641

AN XY:

135632

show subpopulations

Gnomad AFR exome

AF:

0.521

Gnomad AMR exome

AF:

0.384

Gnomad ASJ exome

AF:

0.229

Gnomad EAS exome

AF:

0.532

Gnomad SAS exome

AF:

0.394

Gnomad FIN exome

AF:

0.142

Gnomad NFE exome

AF:

0.179

Gnomad OTH exome

AF:

0.256

GnomAD4 exome

AF:

0.215

AC:

314666

AN:

1461678

Hom.:

41127

Cov.:

AF XY:

0.219

AC XY:

159376

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.537

Gnomad4 AMR exome

AF:

0.381

Gnomad4 ASJ exome

AF:

0.235

Gnomad4 EAS exome

AF:

0.503

Gnomad4 SAS exome

AF:

0.391

Gnomad4 FIN exome

AF:

0.144

Gnomad4 NFE exome

AF:

0.175

Gnomad4 OTH exome

AF:

0.254

GnomAD4 genome

AF:

0.309

AC:

46964

AN:

152042

Hom.:

9156

Cov.:

AF XY:

0.311

AC XY:

23085

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.518

Gnomad4 AMR

AF:

0.356

Gnomad4 ASJ

AF:

0.233

Gnomad4 EAS

AF:

0.511

Gnomad4 SAS

AF:

0.411

Gnomad4 FIN

AF:

0.143

Gnomad4 NFE

AF:

0.176

Gnomad4 OTH

AF:

0.312

Alfa

AF:

0.214

Hom.:

9872

Bravo

AF:

0.337

TwinsUK

AF:

0.167

AC:

619

ALSPAC

AF:

0.172

AC:

662

ESP6500AA

AF:

0.508

AC:

2238

ESP6500EA

AF:

0.179

AC:

1537

ExAC

AF:

0.283

AC:

34356

Asia WGS

AF:

0.516

AC:

1797

AN:

3478

EpiCase

AF:

0.196

EpiControl

AF:

0.194

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.012

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.51

MetaRNN

Benign

0.000026

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.57

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

0.49

REVEL

Benign

0.063

Sift

Benign

0.37

Sift4G

Benign

0.45

Polyphen

0.0

Vest4

0.098

MPC

0.16

ClinPred

0.0023

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.046

gMVP

0.28

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