Genetic Variant TTC14:p.Ile90Phe (chr3-180602997-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_133462.4(TTC14):c.268A>T(p.Ile90Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I90L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TTC14
NM_133462.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.442

Publications

0 publications found

Variant links:

Genes affected

TTC14 (HGNC:24697): (tetratricopeptide repeat domain 14) Predicted to enable nucleic acid binding activity. [provided by Alliance of Genome Resources, Apr 2022]

TTC14 links:

CCDC39 (HGNC:25244): (coiled-coil domain 39 molecular ruler complex subunit) The protein encoded by this gene is involved in the motility of cilia and flagella. The encoded protein is essential for the assembly of dynein regulatory and inner dynein arm complexes, which regulate ciliary beat. Defects in this gene are a cause of primary ciliary dyskinesia type 14 (CILD14). [provided by RefSeq, Jul 2011]

CCDC39 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 14
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CCDC39 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.067025065).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133462.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TTC14	NM_133462.4	MANE Select	c.268A>T	p.Ile90Phe	missense	Exon 2 of 12	NP_597719.1	Q96N46-1
TTC14	NM_001288582.2		c.268A>T	p.Ile90Phe	missense	Exon 2 of 13	NP_001275511.1	Q96N46-2
TTC14	NM_001042601.3		c.268A>T	p.Ile90Phe	missense	Exon 2 of 10	NP_001036066.1	Q96N46-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TTC14	ENST00000296015.9	TSL:1 MANE Select	c.268A>T	p.Ile90Phe	missense	Exon 2 of 12	ENSP00000296015.4	Q96N46-1
TTC14	ENST00000382584.8	TSL:1	c.268A>T	p.Ile90Phe	missense	Exon 2 of 13	ENSP00000372027.4	Q96N46-2
TTC14	ENST00000412756.6	TSL:1	c.268A>T	p.Ile90Phe	missense	Exon 2 of 10	ENSP00000413743.2	Q96N46-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461398

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726950

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33446

American (AMR)

AF:

0.00

AC:

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

86068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111906

Other (OTH)

AF:

0.00

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.040

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.72

M_CAP

Benign

0.016

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

-0.44

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.3

REVEL

Benign

0.045

Sift

Benign

0.083

Sift4G

Benign

0.13

Polyphen

0.0

Vest4

0.13

MutPred

0.13

Gain of glycosylation at S94 (P = 0.0535)

MVP

0.35

MPC

0.26

ClinPred

0.19

GERP RS

-1.3

PromoterAI

0.0027

Neutral

(source)

Varity_R

0.073

gMVP

0.30

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over