chr19-40216191-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152479.6(TTC9B):​c.692G>A​(p.Gly231Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

TTC9B
NM_152479.6 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.887
Variant links:
Genes affected
TTC9B (HGNC:26395): (tetratricopeptide repeat domain 9B)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.056541413).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TTC9BNM_152479.6 linkc.692G>A p.Gly231Glu missense_variant Exon 3 of 3 ENST00000311308.7 NP_689692.2 Q8N6N2-1
TTC9BXM_017026368.2 linkc.*152G>A 3_prime_UTR_variant Exon 3 of 3 XP_016881857.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TTC9BENST00000311308.7 linkc.692G>A p.Gly231Glu missense_variant Exon 3 of 3 1 NM_152479.6 ENSP00000311760.6 Q8N6N2-1
TTC9BENST00000593586.1 linkn.2192G>A non_coding_transcript_exon_variant Exon 1 of 1 6

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152212
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000157
AC:
23
AN:
1461856
Hom.:
0
Cov.:
31
AF XY:
0.00000963
AC XY:
7
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000207
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152212
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000106
Hom.:
0
Bravo
AF:
0.0000151

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.692G>A (p.G231E) alteration is located in exon 3 (coding exon 3) of the TTC9B gene. This alteration results from a G to A substitution at nucleotide position 692, causing the glycine (G) at amino acid position 231 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.087
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
8.0
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0091
T
Eigen
Benign
-0.72
Eigen_PC
Benign
-0.73
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.56
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.057
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
L
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.71
N
REVEL
Benign
0.021
Sift
Benign
0.17
T
Sift4G
Benign
0.93
T
Polyphen
0.0050
B
Vest4
0.11
MVP
0.14
MPC
1.7
ClinPred
0.13
T
GERP RS
2.0
Varity_R
0.075
gMVP
0.26

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: rs916048621; hg19: chr19-40722098; API