rs10502173

Variant names:

• chr11-113332301-C-A
• rs10502173
• NM_017868.4:c.504+2322C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-113332301-C-A
• chr11-113332301-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017868.4(TTC12):​c.504+2322C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,044 control chromosomes in the GnomAD database, including 5,243 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (5243 hom., cov: 32)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC12	NM_017868.4	c.504+2322C>A		intron_variant	Intron 7 of 21	ENST00000529221.6	NP_060338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC12	ENST00000529221.6	c.504+2322C>A		intron_variant	Intron 7 of 21	2	NM_017868.4	ENSP00000433757.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36205 AN: 151926 Hom.: 5226 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.223

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.238 AC: 36262 AN: 152044 Hom.: 5243 Cov.: 32 AF XY: 0.243 AC XY: 18079 AN XY: 74320

African (AFR) AF: 0.371 AC: 15381 AN: 41434

American (AMR) AF: 0.220 AC: 3364 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 539 AN: 3470

East Asian (EAS) AF: 0.491 AC: 2538 AN: 5174

South Asian (SAS) AF: 0.255 AC: 1230 AN: 4816

European-Finnish (FIN) AF: 0.231 AC: 2443 AN: 10570

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10048 AN: 67984

Other (OTH) AF: 0.221 AC: 467 AN: 2110

Alfa AF: 0.153 Hom.: 1224

Bravo AF: 0.244

Asia WGS AF: 0.356 AC: 1238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.56
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10502173; hg19: chr11-113203023;