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GeneBe

9-15187012-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_152574.3(TTC39B):c.1221A>G(p.Ala407=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,613,210 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 10 hom., cov: 33)
Exomes 𝑓: 0.00065 ( 10 hom. )

Consequence

TTC39B
NM_152574.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0700
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-15187012-T-C is Benign according to our data. Variant chr9-15187012-T-C is described in ClinVar as [Benign]. Clinvar id is 776411.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.07 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00645 (983/152328) while in subpopulation AFR AF= 0.0223 (926/41576). AF 95% confidence interval is 0.0211. There are 10 homozygotes in gnomad4. There are 480 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 10 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TTC39BNM_152574.3 linkuse as main transcriptc.1221A>G p.Ala407= synonymous_variant 15/20 ENST00000512701.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TTC39BENST00000512701.7 linkuse as main transcriptc.1221A>G p.Ala407= synonymous_variant 15/202 NM_152574.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00642
AC:
977
AN:
152210
Hom.:
10
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0222
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00308
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00158
AC:
395
AN:
250254
Hom.:
3
AF XY:
0.00115
AC XY:
155
AN XY:
135262
show subpopulations
Gnomad AFR exome
AF:
0.0221
Gnomad AMR exome
AF:
0.000906
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.000656
GnomAD4 exome
AF:
0.000648
AC:
947
AN:
1460882
Hom.:
10
Cov.:
30
AF XY:
0.000566
AC XY:
411
AN XY:
726728
show subpopulations
Gnomad4 AFR exome
AF:
0.0242
Gnomad4 AMR exome
AF:
0.000874
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000349
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00138
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00645
AC:
983
AN:
152328
Hom.:
10
Cov.:
33
AF XY:
0.00644
AC XY:
480
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.0223
Gnomad4 AMR
AF:
0.00307
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00363
Hom.:
1
Bravo
AF:
0.00695
Asia WGS
AF:
0.00202
AC:
7
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeApr 30, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
Cadd
Benign
3.9
Dann
Benign
0.65
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs112186053; hg19: chr9-15187010; API