rs2276070

Positions:

• chr11-113359878-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017868.4(TTC12):​c.1546-62C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,358,820 control chromosomes in the GnomAD database, including 24,330 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3691 hom., cov: 32)
  • Exomes 𝑓: 0.17 (20639 hom.)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.641

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-113359878-C-T is Benign according to our data. Variant chr11-113359878-C-T is described in ClinVar as [Benign]. Clinvar id is 1223951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC12	NM_017868.4	c.1546-62C>T		intron_variant		ENST00000529221.6	NP_060338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC12	ENST00000529221.6	c.1546-62C>T		intron_variant		2	NM_017868.4	ENSP00000433757	A2

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31195 AN: 151892 Hom.: 3687 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.170 AC: 205429 AN: 1206810 Hom.: 20639 AF XY: 0.171 AC XY: 103428 AN XY: 603890

Gnomad4 AFR exome AF: 0.261

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.159

Gnomad4 EAS exome AF: 0.503

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.205 AC: 31217 AN: 152010 Hom.: 3691 Cov.: 32 AF XY: 0.211 AC XY: 15661 AN XY: 74284

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.182

Alfa AF: 0.152 Hom.: 2025

Bravo AF: 0.206

Asia WGS AF: 0.322 AC: 1117 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.44

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

Other links and lift over

dbSNP: rs2276070; hg19: chr11-113230600; COSMIC: COSV59097892; COSMIC: COSV59097892;