Genetic Variant TTC3:c.688-6T>C (chr21-37095344-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_001330683.2(TTC3):c.688-6T>C variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000357 in 1,592,128 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

TTC3
NM_001330683.2 splice_region, intron

Scores

Splicing: ADA: 0.01335

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.62

Publications

0 publications found

Variant links:

Genes affected

TTC3 (HGNC:12393): (tetratricopeptide repeat domain 3) Enables ubiquitin-protein transferase activity. Involved in protein K48-linked ubiquitination and ubiquitin-dependent protein catabolic process. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TTC3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 21-37095344-T-C is Benign according to our data. Variant chr21-37095344-T-C is described in ClinVar as Benign. ClinVar VariationId is 769126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330683.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TTC3	NM_001330683.2	MANE Select	c.688-6T>C	splice_region intron	N/A	NP_001317612.1	P53804-1
TTC3	NM_001320703.2		c.754-6T>C	splice_region intron	N/A	NP_001307632.1
TTC3	NM_001320704.2		c.688-6T>C	splice_region intron	N/A	NP_001307633.1	H7BZ57

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TTC3	ENST00000418766.6	TSL:5 MANE Select	c.688-6T>C	splice_region intron	N/A	ENSP00000403943.2	P53804-1
TTC3	ENST00000354749.6	TSL:1	c.688-6T>C	splice_region intron	N/A	ENSP00000346791.2	P53804-1
TTC3	ENST00000399017.6	TSL:1	c.688-6T>C	splice_region intron	N/A	ENSP00000381981.2	P53804-1

Frequencies

GnomAD3 genomes

AF:

0.00145

AC:

221

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00488

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000787

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:

0.0000882

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000496

AC:

117

AN:

235656

AF XY:

0.000447

show subpopulations

Gnomad AFR exome

AF:

0.00550

Gnomad AMR exome

AF:

0.000424

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000129

Gnomad OTH exome

AF:

0.000535

GnomAD4 exome

AF:

0.000240

AC:

346

AN:

1439872

Hom.:

Cov.:

AF XY:

0.000234

AC XY:

168

AN XY:

716480

show subpopulations

African (AFR)

AF:

0.00655

AC:

211

AN:

32214

American (AMR)

AF:

0.000583

AC:

AN:

41136

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25360

East Asian (EAS)

AF:

0.00

AC:

AN:

39214

South Asian (SAS)

AF:

0.0000483

AC:

AN:

82838

European-Finnish (FIN)

AF:

0.000301

AC:

AN:

53072

Middle Eastern (MID)

AF:

0.00339

AC:

AN:

4714

European-Non Finnish (NFE)

AF:

0.0000290

AC:

AN:

1101982

Other (OTH)

AF:

0.000725

AC:

AN:

59342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.00146

AC:

223

AN:

152256

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

111

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00491

AC:

204

AN:

41542

American (AMR)

AF:

0.000786

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68032

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.000573

Hom.:

Bravo

AF:

0.00170

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

4.6

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.013

dbscSNV1_RF

Benign

0.40

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