Variant chr1-156581962-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001105669.4(TTC24):c.598G>A(p.Ala200Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000094 in 1,383,544 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. A200S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000094 ( 0 hom. )

Consequence

TTC24
NM_001105669.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.11

Variant links:

Genes affected

TTC24 (HGNC:32348): (tetratricopeptide repeat domain 24)

TTC24 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36302364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC24	NM_001105669.4 linkuse as main transcript	c.598G>A	p.Ala200Thr	missense_variant	2/11	ENST00000368236.8	NP_001099139.2	A2A3L6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC24	ENST00000368236.8 linkuse as main transcript	c.598G>A	p.Ala200Thr	missense_variant	2/11	5	NM_001105669.4	ENSP00000357219.3		A2A3L6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000769

AC:

AN:

130108

Hom.:

AF XY:

0.0000142

AC XY:

AN XY:

70292

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:

0.0000504

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000940

AC:

AN:

1383544

Hom.:

Cov.:

AF XY:

0.0000117

AC XY:

AN XY:

682058

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:

0.000169

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 19, 2023

The c.598G>A (p.A200T) alteration is located in exon 2 (coding exon 1) of the TTC24 gene. This alteration results from a G to A substitution at nucleotide position 598, causing the alanine (A) at amino acid position 200 to be replaced by a threonine (T). 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

0.13

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0018

T;T

Eigen

Benign

0.16

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.70

T;.

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.36

T;T

MetaSVM

Uncertain

-0.27

MutationAssessor

Uncertain

2.3

M;M

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.7

N;N

REVEL

Uncertain

0.33

Sift

Benign

0.10

T;T

Sift4G

Pathogenic

0.0

D;D

Vest4

0.45

MutPred

0.36

Loss of disorder (P = 0.0995);Loss of disorder (P = 0.0995);

MVP

0.60

MPC

0.44

ClinPred

0.92

GERP RS

4.6

Varity_R

0.11

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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