NM_017868.4:c.1816+30T>C

Variant names:

• chr11-113363957-T-C
• rs719802
• NM_017868.4:c.1816+30T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017868.4(TTC12):​c.1816+30T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 1,509,252 control chromosomes in the GnomAD database, including 269,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (23090 hom., cov: 34)
  • Exomes 𝑓: 0.60 (246782 hom.)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.15
• Publications: 33 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-113363957-T-C is Benign according to our data. Variant chr11-113363957-T-C is described in ClinVar as Benign. ClinVar VariationId is 1280036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC12	NM_017868.4	c.1816+30T>C		intron_variant	Intron 20 of 21	ENST00000529221.6	NP_060338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC12	ENST00000529221.6	c.1816+30T>C		intron_variant	Intron 20 of 21	2	NM_017868.4	ENSP00000433757.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82283 AN: 152096 Hom.: 23083 Cov.: 34

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.574

GnomAD2 exomes AF: 0.565 AC: 136094 AN: 240964 AF XY: 0.574

Gnomad AFR exome AF: 0.395

Gnomad AMR exome AF: 0.424

Gnomad ASJ exome AF: 0.629

Gnomad EAS exome AF: 0.525

Gnomad FIN exome AF: 0.658

Gnomad NFE exome AF: 0.623

Gnomad OTH exome AF: 0.593

GnomAD4 exome AF: 0.600 AC: 813611 AN: 1357038 Hom.: 246782 Cov.: 19 AF XY: 0.600 AC XY: 408048 AN XY: 680288

African (AFR) AF: 0.392 AC: 12239 AN: 31228

American (AMR) AF: 0.439 AC: 19230 AN: 43808

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 15945 AN: 25176

East Asian (EAS) AF: 0.545 AC: 21197 AN: 38926

South Asian (SAS) AF: 0.536 AC: 44330 AN: 82648

European-Finnish (FIN) AF: 0.658 AC: 34778 AN: 52850

Middle Eastern (MID) AF: 0.577 AC: 3214 AN: 5570

European-Non Finnish (NFE) AF: 0.617 AC: 628926 AN: 1019936

Other (OTH) AF: 0.593 AC: 33752 AN: 56896

GnomAD4 genome AF: 0.541 AC: 82324 AN: 152214 Hom.: 23090 Cov.: 34 AF XY: 0.541 AC XY: 40270 AN XY: 74412

African (AFR) AF: 0.402 AC: 16685 AN: 41544

American (AMR) AF: 0.486 AC: 7439 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2144 AN: 3470

East Asian (EAS) AF: 0.529 AC: 2740 AN: 5176

South Asian (SAS) AF: 0.515 AC: 2490 AN: 4832

European-Finnish (FIN) AF: 0.654 AC: 6924 AN: 10590

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.617 AC: 41917 AN: 67984

Other (OTH) AF: 0.570 AC: 1207 AN: 2116

Alfa AF: 0.596 Hom.: 81550

Bravo AF: 0.524

Asia WGS AF: 0.456 AC: 1586 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ciliary dyskinesia, primary, 45 Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.47
DANN	Benign	0.28
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs719802; hg19: chr11-113234679; COSMIC: COSV59099686; COSMIC: COSV59099686;