Variant 11-113323414-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017868.4(TTC12):c.185A>G(p.Asn62Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000676 in 1,611,336 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

TTC12
NM_017868.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.26

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.041915298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC12	NM_017868.4 linkuse as main transcript	c.185A>G	p.Asn62Ser	missense_variant	3/22	ENST00000529221.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC12	ENST00000529221.6 linkuse as main transcript	c.185A>G	p.Asn62Ser	missense_variant	3/22	2	NM_017868.4	A2	Q9H892-1

Frequencies

GnomAD3 genomes

AF:

0.000361

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000121

AC:

AN:

248186

Hom.:

AF XY:

0.0000819

AC XY:

AN XY:

134304

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.000298

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000343

AC:

AN:

1459048

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

725954

show subpopulations

Gnomad4 AFR exome

AF:

0.000961

Gnomad4 AMR exome

AF:

0.000251

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:

0.00000180

Gnomad4 OTH exome

AF:

0.0000830

GnomAD4 genome

AF:

0.000387

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000783

Hom.:

Bravo

AF:

0.000427

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000988

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2024

The c.185A>G (p.N62S) alteration is located in exon 3 (coding exon 2) of the TTC12 gene. This alteration results from a A to G substitution at nucleotide position 185, causing the asparagine (N) at amino acid position 62 to be replaced by a serine (S). 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

0.14

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

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

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

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

M_CAP

Benign

0.011

MetaRNN

Benign

0.042

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

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.7

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

MutationTaster

Benign

0.51

D;D;D;D

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.8

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

REVEL

Benign

0.11

Sift

Uncertain

0.0090

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

Sift4G

Benign

0.15

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

Polyphen

0.79

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

Vest4

0.27

MVP

0.67

MPC

0.31

ClinPred

0.058

GERP RS

5.0

Varity_R

0.13

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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