5-34867014-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_144725.4(TTC23L):​c.785C>T​(p.Ala262Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,612,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TTC23L
NM_144725.4 missense

Scores

8
6
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.08
Variant links:
Genes affected
TTC23L (HGNC:26355): (tetratricopeptide repeat domain 23 like) Predicted to be located in cytoplasm; microtubule cytoskeleton; and midbody. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.794

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TTC23LNM_144725.4 linkc.785C>T p.Ala262Val missense_variant Exon 7 of 11 ENST00000505624.6 NP_653326.3 Q6PF05-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TTC23LENST00000505624.6 linkc.785C>T p.Ala262Val missense_variant Exon 7 of 11 1 NM_144725.4 ENSP00000422188.1 Q6PF05-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152236
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000408
AC:
1
AN:
245006
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
132806
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00000901
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000343
AC:
5
AN:
1459838
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
725948
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:
0.00000270
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152236
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.00000827
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.785C>T (p.A262V) alteration is located in exon 7 (coding exon 6) of the TTC23L gene. This alteration results from a C to T substitution at nucleotide position 785, causing the alanine (A) at amino acid position 262 to be replaced by a valine (V). 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
Pathogenic
0.64
BayesDel_addAF
Pathogenic
0.36
D
BayesDel_noAF
Pathogenic
0.28
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.22
T;.;.;.
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Benign
0.86
D;D;D;D
M_CAP
Benign
0.070
D
MetaRNN
Pathogenic
0.79
D;D;D;D
MetaSVM
Uncertain
0.41
D
MutationAssessor
Uncertain
2.0
M;.;M;.
PrimateAI
Benign
0.43
T
PROVEAN
Uncertain
-2.9
D;.;.;.
REVEL
Pathogenic
0.66
Sift
Pathogenic
0.0
D;.;.;.
Sift4G
Pathogenic
0.0
D;.;D;.
Polyphen
1.0
D;.;D;.
Vest4
0.87
MutPred
0.67
Loss of disorder (P = 0.0615);Loss of disorder (P = 0.0615);Loss of disorder (P = 0.0615);Loss of disorder (P = 0.0615);
MVP
0.81
MPC
0.49
ClinPred
0.98
D
GERP RS
5.3
Varity_R
0.68
gMVP
0.55

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: rs776576080; hg19: chr5-34867119; API