Genetic Variant NM_001008237.3:c.129C>T (chr2-19901726-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001008237.3(TTC32):c.129C>T(p.Ser43Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,613,186 control chromosomes in the GnomAD database, including 33,035 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 0.20 ( 3402 hom., cov: 33)

Exomes 𝑓: 0.19 ( 29633 hom. )

Consequence

TTC32
NM_001008237.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.13

Publications

14 publications found

Variant links:

Genes affected

TTC32 (HGNC:32954): (tetratricopeptide repeat domain 32)

TTC32 links:

TTC32-DT (HGNC:55236): (TTC32 divergent transcript)

TTC32-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP7

Synonymous conserved (PhyloP=-2.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC32	NM_001008237.3 link	c.129C>T	p.Ser43Ser	synonymous_variant	Exon 1 of 3	ENST00000333610.4	NP_001008238.1	Q5I0X7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC32	ENST00000333610.4 link	c.129C>T	p.Ser43Ser	synonymous_variant	Exon 1 of 3	1	NM_001008237.3	ENSP00000333018.3		Q5I0X7

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30644

AN:

152096

Hom.:

3397

Cov.:

show subpopulations

Gnomad AFR

AF:

0.212

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.236

Gnomad ASJ

AF:

0.156

Gnomad EAS

AF:

0.411

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.216

GnomAD2 exomes

AF:

0.219

AC:

54574

AN:

249548

AF XY:

0.225

show subpopulations

Gnomad AFR exome

AF:

0.216

Gnomad AMR exome

AF:

0.198

Gnomad ASJ exome

AF:

0.153

Gnomad EAS exome

AF:

0.418

Gnomad FIN exome

AF:

0.164

Gnomad NFE exome

AF:

0.164

Gnomad OTH exome

AF:

0.210

GnomAD4 exome

AF:

0.188

AC:

274351

AN:

1460972

Hom.:

29633

Cov.:

AF XY:

0.194

AC XY:

140753

AN XY:

726676

show subpopulations

African (AFR)

AF:

0.216

AC:

7225

AN:

33454

American (AMR)

AF:

0.201

AC:

8975

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.158

AC:

4132

AN:

26126

East Asian (EAS)

AF:

0.435

AC:

17268

AN:

39678

South Asian (SAS)

AF:

0.385

AC:

33164

AN:

86168

European-Finnish (FIN)

AF:

0.161

AC:

8587

AN:

53362

Middle Eastern (MID)

AF:

0.287

AC:

1647

AN:

5748

European-Non Finnish (NFE)

AF:

0.163

AC:

181346

AN:

1111408

Other (OTH)

AF:

0.199

AC:

12007

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

12903

25806

38710

51613

64516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6756

13512

20268

27024

33780

<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:

0.202

AC:

30685

AN:

152214

Hom.:

3402

Cov.:

AF XY:

0.207

AC XY:

15390

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.212

AC:

8825

AN:

41544

American (AMR)

AF:

0.237

AC:

3620

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

540

AN:

3468

East Asian (EAS)

AF:

0.410

AC:

2111

AN:

5148

South Asian (SAS)

AF:

0.379

AC:

1829

AN:

4828

European-Finnish (FIN)

AF:

0.161

AC:

1711

AN:

10606

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.167

AC:

11370

AN:

68008

Other (OTH)

AF:

0.217

AC:

457

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1282

2565

3847

5130

6412

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.161

Hom.:

1941

Bravo

AF:

0.202

Asia WGS

AF:

0.411

AC:

1426

AN:

3478

EpiCase

AF:

0.179

EpiControl

AF:

0.179

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.4

(source)

DANN

Benign

0.80

PhyloP100

-2.1

PromoterAI

-0.11

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over