Genetic Variant TTC39C:p.Met39Val (chr18-24014986-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001135993.2(TTC39C):c.115A>G(p.Met39Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 1,528,152 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

TTC39C
NM_001135993.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.04

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.115A>G	p.Met39Val	missense	Exon 1 of 14	NP_001129465.1	Q8N584-1
TTC39C	NM_001243425.2		c.115A>G	p.Met39Val	missense	Exon 1 of 2	NP_001230354.1	Q8N584-3
TTC39C	NM_153211.4		c.-17+21948A>G		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.115A>G	p.Met39Val	missense	Exon 1 of 14	ENSP00000323645.3	Q8N584-1
TTC39C	ENST00000584250.2	TSL:1	c.115A>G	p.Met39Val	missense	Exon 1 of 2	ENSP00000464344.1	Q8N584-3
TTC39C	ENST00000304621.10	TSL:1	c.-17+21948A>G		intron	N/A	ENSP00000306598.6	Q8N584-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151980

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:

0.0000294

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000155

AC:

AN:

129366

AF XY:

0.0000143

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:

0.0000404

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000378

AC:

AN:

1376172

Hom.:

Cov.:

AF XY:

0.0000412

AC XY:

AN XY:

678832

show subpopulations

African (AFR)

AF:

0.0000349

AC:

AN:

28630

American (AMR)

AF:

0.00

AC:

AN:

32492

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24344

East Asian (EAS)

AF:

0.00

AC:

AN:

33176

South Asian (SAS)

AF:

0.00

AC:

AN:

76686

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48546

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5630

European-Non Finnish (NFE)

AF:

0.0000467

AC:

AN:

1069778

Other (OTH)

AF:

0.0000176

AC:

AN:

56890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

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:

0.0000197

AC:

AN:

151980

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41414

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67948

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

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:

0.0000387

Hom.:

Bravo

AF:

0.0000340

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

Pathogenic

0.68

BayesDel_addAF

Uncertain

0.052

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.069

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.90

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.4

PhyloP100

3.0

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.33

Sift

Uncertain

0.015

Sift4G

Pathogenic

0.0

Polyphen

0.84

Vest4

0.58

MutPred

0.77

Loss of catalytic residue at M39 (P = 0.0347)

MVP

0.36

MPC

0.64

ClinPred

0.59

GERP RS

3.6

PromoterAI

-0.17

Neutral

(source)

Varity_R

0.47

gMVP

0.63

Mutation Taster

=71/29

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over