rs781810431

Variant names:

• chr11-113316283-T-C
• rs781810431
• NM_017868.4:c.26T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-113316283-T-C
• chr11-113316283-T-G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_017868.4(TTC12):​c.26T>C​(p.Leu9Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000454 in 1,321,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. L9W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: TTC12 NM_017868.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.90
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 45

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.31247145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC12	NM_017868.4	c.26T>C	p.Leu9Ser	missense_variant	Exon 2 of 22	ENST00000529221.6	NP_060338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC12	ENST00000529221.6	c.26T>C	p.Leu9Ser	missense_variant	Exon 2 of 22	2	NM_017868.4	ENSP00000433757.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000454 AC: 6 AN: 1321712 Hom.: 0 Cov.: 26 AF XY: 0.00000460 AC XY: 3 AN XY: 652288

African (AFR) AF: 0.00 AC: 0 AN: 28860

American (AMR) AF: 0.00 AC: 0 AN: 28252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21144

East Asian (EAS) AF: 0.00 AC: 0 AN: 35916

South Asian (SAS) AF: 0.00 AC: 0 AN: 57516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48496

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5168

European-Non Finnish (NFE) AF: 0.00000576 AC: 6 AN: 1042338

Other (OTH) AF: 0.00 AC: 0 AN: 54022

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	27
DANN	Uncertain	1.0
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.81	T
PhyloP100		3.9
PROVEAN	Benign	0.010	N
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D
MutPred		0.25		Gain of disorder (P = 0.0087);
MVP		0.52
ClinPred		0.92	D
GERP RS		4.9
PromoterAI		0.033	Neutral
Varity_R		0.15
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs781810431; hg19: chr11-113187005;