Genetic Variant TTC39C:p.Ser4Leu (chr18-24014882-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001135993.2(TTC39C):c.11C>T(p.Ser4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000562 in 1,424,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000047 ( 0 hom. )

Consequence

TTC39C
NM_001135993.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.15

Publications

0 publications found

Variant links:

Genes affected

TTC39C (HGNC:26595): (tetratricopeptide repeat domain 39C) Predicted to be involved in cilium assembly and otolith morphogenesis. [provided by Alliance of Genome Resources, Apr 2022]

TTC39C links:

TTC39C-AS1 (HGNC:51321): (TTC39C antisense RNA 1)

TTC39C-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15705624).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135993.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TTC39C	NM_001135993.2	MANE Select	c.11C>T	p.Ser4Leu	missense	Exon 1 of 14	NP_001129465.1	Q8N584-1
TTC39C	NM_001243425.2		c.11C>T	p.Ser4Leu	missense	Exon 1 of 2	NP_001230354.1	Q8N584-3
TTC39C	NM_153211.4		c.-17+21844C>T		intron	N/A	NP_694943.2	Q8N584-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TTC39C	ENST00000317571.8	TSL:1 MANE Select	c.11C>T	p.Ser4Leu	missense	Exon 1 of 14	ENSP00000323645.3	Q8N584-1
TTC39C	ENST00000584250.2	TSL:1	c.11C>T	p.Ser4Leu	missense	Exon 1 of 2	ENSP00000464344.1	Q8N584-3
TTC39C	ENST00000304621.10	TSL:1	c.-17+21844C>T		intron	N/A	ENSP00000306598.6	Q8N584-2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151594

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000204

AC:

AN:

48914

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000563

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000472

AC:

AN:

1272484

Hom.:

Cov.:

AF XY:

0.00000320

AC XY:

AN XY:

624616

show subpopulations

African (AFR)

AF:

0.0000409

AC:

AN:

24438

American (AMR)

AF:

0.00

AC:

AN:

15972

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18462

East Asian (EAS)

AF:

0.00

AC:

AN:

27962

South Asian (SAS)

AF:

0.00

AC:

AN:

60710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44920

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4922

European-Non Finnish (NFE)

AF:

0.00000489

AC:

AN:

1023298

Other (OTH)

AF:

0.00

AC:

AN:

51800

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

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

AF:

0.0000132

AC:

AN:

151594

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74030

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41336

American (AMR)

AF:

0.00

AC:

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10470

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67840

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.026

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.78

M_CAP

Pathogenic

0.50

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

3.1

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.0

REVEL

Benign

0.032

Sift

Benign

0.12

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.10

MutPred

0.19

Loss of phosphorylation at S4 (P = 0.0157)

MVP

0.25

MPC

0.42

ClinPred

0.21

GERP RS

3.6

PromoterAI

-0.048

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.094

gMVP

0.45

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over