dbSNP rs2305024: TTC39C:c.816-61A>C (chr18-24082852-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001135993.2(TTC39C):c.816-61A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.909 in 1,493,744 control chromosomes in the GnomAD database, including 623,490 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.82 ( 53783 hom., cov: 31)

Exomes 𝑓: 0.92 ( 569707 hom. )

Consequence

TTC39C
NM_001135993.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.792

Publications

6 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:

ENSG00000265204 (HGNC:):

ENSG00000265204 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001135993.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC39C	NM_001135993.2	MANE Select	c.816-61A>C		intron	N/A	NP_001129465.1	Q8N584-1
	TTC39C	NM_153211.4		c.633-61A>C		intron	N/A	NP_694943.2	Q8N584-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TTC39C	ENST00000317571.8	TSL:1 MANE Select	c.816-61A>C	intron	N/A	ENSP00000323645.3	Q8N584-1
TTC39C	ENST00000304621.10	TSL:1	c.633-61A>C	intron	N/A	ENSP00000306598.6	Q8N584-2
TTC39C	ENST00000919100.1		c.816-61A>C	intron	N/A	ENSP00000589159.1

Frequencies

GnomAD3 genomes

AF:

0.825

AC:

125391

AN:

151998

Hom.:

53782

Cov.:

show subpopulations

Gnomad AFR

AF:

0.570

Gnomad AMI

AF:

0.924

Gnomad AMR

AF:

0.906

Gnomad ASJ

AF:

0.937

Gnomad EAS

AF:

0.781

Gnomad SAS

AF:

0.771

Gnomad FIN

AF:

0.964

Gnomad MID

AF:

0.902

Gnomad NFE

AF:

0.939

Gnomad OTH

AF:

0.850

GnomAD4 exome

AF:

0.919

AC:

1232292

AN:

1341628

Hom.:

569707

AF XY:

0.916

AC XY:

602091

AN XY:

657320

show subpopulations

African (AFR)

AF:

0.552

AC:

16577

AN:

30014

American (AMR)

AF:

0.944

AC:

30849

AN:

32672

Ashkenazi Jewish (ASJ)

AF:

0.935

AC:

19564

AN:

20930

East Asian (EAS)

AF:

0.795

AC:

30054

AN:

37796

South Asian (SAS)

AF:

0.784

AC:

50851

AN:

64840

European-Finnish (FIN)

AF:

0.959

AC:

46763

AN:

48776

Middle Eastern (MID)

AF:

0.878

AC:

4620

AN:

5260

European-Non Finnish (NFE)

AF:

0.940

AC:

983853

AN:

1046424

Other (OTH)

AF:

0.895

AC:

49161

AN:

54916

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

4817

9633

14450

19266

24083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21278

42556

63834

85112

106390

<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:

0.825

AC:

125421

AN:

152116

Hom.:

53783

Cov.:

AF XY:

0.825

AC XY:

61381

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.569

AC:

23565

AN:

41396

American (AMR)

AF:

0.907

AC:

13865

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.937

AC:

3251

AN:

3468

East Asian (EAS)

AF:

0.781

AC:

4040

AN:

5172

South Asian (SAS)

AF:

0.772

AC:

3723

AN:

4822

European-Finnish (FIN)

AF:

0.964

AC:

10241

AN:

10618

Middle Eastern (MID)

AF:

0.895

AC:

263

AN:

294

European-Non Finnish (NFE)

AF:

0.939

AC:

63854

AN:

68028

Other (OTH)

AF:

0.841

AC:

1776

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

922

1843

2765

3686

4608

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

866

1732

2598

3464

4330

<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:

0.884

Hom.:

93670

Bravo

AF:

0.812

Asia WGS

AF:

0.709

AC:

2469

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.4

(source)

DANN

Benign

0.67

PhyloP100

0.79

Mutation Taster

=100/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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