dbSNP rs151257967: TTC12:p.Thr59Asn (chr11-113323405-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_017868.4(TTC12):c.176C>A(p.Thr59Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T59I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TTC12
NM_017868.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.38

Variant links:

Genes affected

TTC12 (HGNC:23700): (tetratricopeptide repeat domain 12) Involved in axonemal dynein complex assembly and sperm axoneme assembly. Located in centrosome and cytoplasm. Implicated in primary ciliary dyskinesia 45. [provided by Alliance of Genome Resources, Apr 2022]

TTC12 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=0.20837793).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC12	NM_017868.4 link	c.176C>A	p.Thr59Asn	missense_variant	Exon 3 of 22	ENST00000529221.6	NP_060338.3	Q9H892-1A8K8G6Q53G14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC12	ENST00000529221.6 link	c.176C>A	p.Thr59Asn	missense_variant	Exon 3 of 22	2	NM_017868.4	ENSP00000433757.1		Q9H892-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

249782

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135112

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:

0.0000265

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1460162

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726454

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000174

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.078

T;T;T;.;.;.;T;.;.;.

Eigen

Benign

0.19

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.88

D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.0095

MetaRNN

Benign

0.21

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.7

M;.;.;.;.;.;.;.;M;.

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.6

D;D;D;D;N;D;D;D;N;N

REVEL

Benign

0.086

Sift

Uncertain

0.0090

D;D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.0080

D;D;D;T;T;D;D;D;D;D

Polyphen

0.93

P;.;.;.;.;.;.;.;.;.

Vest4

0.42

MutPred

0.11

Loss of glycosylation at T59 (P = 0.1117);Loss of glycosylation at T59 (P = 0.1117);Loss of glycosylation at T59 (P = 0.1117);.;Loss of glycosylation at T59 (P = 0.1117);Loss of glycosylation at T59 (P = 0.1117);Loss of glycosylation at T59 (P = 0.1117);Loss of glycosylation at T59 (P = 0.1117);Loss of glycosylation at T59 (P = 0.1117);Loss of glycosylation at T59 (P = 0.1117);

MVP

0.58

MPC

0.37

ClinPred

0.90

GERP RS

3.1

Varity_R

0.24

gMVP

0.51

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over