Genetic Variant TTC23L:p.Ile264Thr (chr5-34867020-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_144725.4(TTC23L):c.791T>C(p.Ile264Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000651 in 1,612,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. I264M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

TTC23L
NM_144725.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

Publications

0 publications found

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:

ENSG00000302680 (HGNC:):

ENSG00000302680 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3055993).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144725.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TTC23L	NM_144725.4	MANE Select	c.791T>C	p.Ile264Thr	missense	Exon 7 of 11	NP_653326.3
TTC23L	NM_001386170.1		c.791T>C	p.Ile264Thr	missense	Exon 7 of 11	NP_001373099.1
TTC23L	NM_001386171.1		c.818T>C	p.Ile273Thr	missense	Exon 7 of 10	NP_001373100.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TTC23L	ENST00000505624.6	TSL:1 MANE Select	c.791T>C	p.Ile264Thr	missense	Exon 7 of 11	ENSP00000422188.1	Q6PF05-1
TTC23L	ENST00000610313.1	TSL:1	c.791T>C	p.Ile264Thr	missense	Exon 6 of 7	ENSP00000484792.1	Q6PF05-2
TTC23L	ENST00000514080.2	TSL:2	c.791T>C	p.Ile264Thr	missense	Exon 6 of 10	ENSP00000497109.1	A0A3B3IS63

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000816

AC:

AN:

245144

AF XY:

0.00000753

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000692

AC:

101

AN:

1459872

Hom.:

Cov.:

AF XY:

0.0000592

AC XY:

AN XY:

725966

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44476

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39602

South Asian (SAS)

AF:

0.00

AC:

AN:

85710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53256

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

1111200

Other (OTH)

AF:

0.0000332

AC:

AN:

60292

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

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41466

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000579

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000827

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Uncertain

0.017

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.083

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.77

M_CAP

Benign

0.049

MetaRNN

Benign

0.31

MetaSVM

Uncertain

-0.25

MutationAssessor

Benign

2.0

PhyloP100

1.8

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.44

Sift

Benign

0.031

Sift4G

Uncertain

0.0060

Polyphen

0.49

Vest4

0.81

MVP

0.74

MPC

0.28

ClinPred

0.84

GERP RS

5.3

Varity_R

0.11

gMVP

0.28

Mutation Taster

=85/15

polymorphism

(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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over