dbSNP rs7874043: TTC39B:c.*299T>G (chr9-15249433-A-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.*299T>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 0.0413 in 152,860 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.041 ( 159 hom., cov: 32)

Exomes 𝑓: 0.017 ( 0 hom. )

Consequence

TTC39B
ENST00000506891.1 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.890

Publications

6 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=-0.7).

BP6

Variant 9-15249433-A-C is Benign according to our data. Variant chr9-15249433-A-C is described in ClinVar as Benign. ClinVar VariationId is 1225250.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+18481T>G	intron	N/A	NP_689787.3	A0A8V8PNE1
TTC39B	NM_001168339.2		c.77+18481T>G	intron	N/A	NP_001161811.2
TTC39B	NM_001168340.2		c.77+18481T>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.*299T>G	3_prime_UTR	Exon 4 of 4	ENSP00000427314.2	H0YAJ6
TTC39B	ENST00000512701.7	TSL:2 MANE Select	c.77+18481T>G	intron	N/A	ENSP00000422496.2	A0A8V8PNE1
TTC39B	ENST00000505732.5	TSL:1	n.312+18481T>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0413

AC:

6290

AN:

152152

Hom.:

160

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0644

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0416

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.0624

Gnomad SAS

AF:

0.0462

Gnomad FIN

AF:

0.0524

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0254

Gnomad OTH

AF:

0.0435

GnomAD4 exome

AF:

0.0170

AC:

AN:

588

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

AN XY:

392

show subpopulations

African (AFR)

AF:

0.0833

AC:

AN:

American (AMR)

AF:

0.100

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0714

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0102

AC:

AN:

488

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0414

AC:

6302

AN:

152272

Hom.:

159

Cov.:

AF XY:

0.0434

AC XY:

3232

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0645

AC:

2679

AN:

41544

American (AMR)

AF:

0.0416

AC:

636

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0176

AC:

AN:

3470

East Asian (EAS)

AF:

0.0621

AC:

322

AN:

5184

South Asian (SAS)

AF:

0.0469

AC:

226

AN:

4822

European-Finnish (FIN)

AF:

0.0524

AC:

556

AN:

10602

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0254

AC:

1725

AN:

68032

Other (OTH)

AF:

0.0426

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

306

613

919

1226

1532

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:

0.0317

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

-0.70

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

0.89

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