Genetic Variant TTC39B:c.*680A>G (chr9-15249052-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000506891.1(TTC39B):c.*680A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0415 in 152,296 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.041 ( 162 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

TTC39B
ENST00000506891.1 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.724

Publications

4 publications found

Variant links:

Genes affected

TTC39B (HGNC:23704): (tetratricopeptide repeat domain 39B) Predicted to be involved in several processes, including cholesterol homeostasis; negative regulation of cholesterol storage; and regulation of cholesterol efflux. [provided by Alliance of Genome Resources, Apr 2022]

TTC39B links:

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new If you want to explore the variant's impact on the transcript ENST00000506891.1, 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 9-15249052-T-C is Benign according to our data. Variant chr9-15249052-T-C is described in ClinVar as Benign. ClinVar VariationId is 1244123.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0624 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000506891.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TTC39B	NM_152574.3	MANE Select	c.77+18862A>G	intron	N/A	NP_689787.3	A0A8V8PNE1
TTC39B	NM_001168339.2		c.77+18862A>G	intron	N/A	NP_001161811.2
TTC39B	NM_001168340.2		c.77+18862A>G	intron	N/A	NP_001161812.2	A0A8V8NCV2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TTC39B	ENST00000506891.1	TSL:1	c.*680A>G	3_prime_UTR	Exon 4 of 4	ENSP00000427314.2	H0YAJ6
TTC39B	ENST00000512701.7	TSL:2 MANE Select	c.77+18862A>G	intron	N/A	ENSP00000422496.2	A0A8V8PNE1
TTC39B	ENST00000505732.5	TSL:1	n.312+18862A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0414

AC:

6301

AN:

152178

Hom.:

163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0644

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0415

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.0627

Gnomad SAS

AF:

0.0464

Gnomad FIN

AF:

0.0531

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0254

Gnomad OTH

AF:

0.0435

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0415

AC:

6313

AN:

152296

Hom.:

162

Cov.:

AF XY:

0.0435

AC XY:

3238

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0645

AC:

2680

AN:

41564

American (AMR)

AF:

0.0415

AC:

635

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0176

AC:

AN:

3468

East Asian (EAS)

AF:

0.0625

AC:

324

AN:

5184

South Asian (SAS)

AF:

0.0470

AC:

227

AN:

4826

European-Finnish (FIN)

AF:

0.0531

AC:

563

AN:

10604

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0254

AC:

1726

AN:

68024

Other (OTH)

AF:

0.0425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

315

630

946

1261

1576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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:

0.0292

Hom.:

Bravo

AF:

0.0406

Asia WGS

AF:

0.0510

AC:

178

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.3

(source)

DANN

Benign

0.70

PhyloP100

0.72

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over