Variant chr5-34845636-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144725.4(TTC23L):c.218C>T(p.Ser73Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,460,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S73Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

TTC23L
NM_144725.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.162

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]

TTC23L links:

LOC124900959 (HGNC:):

LOC124900959 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14856136).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC23L	NM_144725.4 linkuse as main transcript	c.218C>T	p.Ser73Phe	missense_variant	3/11	ENST00000505624.6
LOC124900959	XR_007058729.1 linkuse as main transcript	n.582-2530G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC23L	ENST00000505624.6 linkuse as main transcript	c.218C>T	p.Ser73Phe	missense_variant	3/11	1	NM_144725.4	A2	Q6PF05-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

247702

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134380

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:

0.0000990

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1460834

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726650

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:

0.0000930

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2021

The c.218C>T (p.S73F) alteration is located in exon 3 (coding exon 2) of the TTC23L gene. This alteration results from a C to T substitution at nucleotide position 218, causing the serine (S) at amino acid position 73 to be replaced by a phenylalanine (F). 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

0.26

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0064

T;.;.;.

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.80

T;T;T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.;M;.

MutationTaster

Benign

0.93

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.3

N;.;.;.

REVEL

Benign

0.12

Sift

Benign

0.039

D;.;.;.

Sift4G

Pathogenic

0.0

D;.;D;.

Polyphen

0.96

D;.;.;.

Vest4

0.29

MutPred

0.38

Loss of phosphorylation at S73 (P = 0.026);Loss of phosphorylation at S73 (P = 0.026);Loss of phosphorylation at S73 (P = 0.026);Loss of phosphorylation at S73 (P = 0.026);

MVP

0.38

MPC

0.47

ClinPred

0.78

GERP RS

3.0

Varity_R

0.080

gMVP

0.32

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over