NM_017868.4:c.1546-62C>T

Variant names:

• chr11-113359878-C-T
• rs2276070
• NM_017868.4:c.1546-62C>T

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.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
• Publications: 7 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=-0.87).
• BP6: Variant 11-113359878-C-T is Benign according to our data. Variant chr11-113359878-C-T is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017868.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC12	NM_017868.4	MANE Select	c.1546-62C>T		intron	N/A	NP_060338.3
	TTC12	NM_001318533.2		c.1564-62C>T		intron	N/A	NP_001305462.1
	TTC12	NM_001378063.1		c.1549-62C>T		intron	N/A	NP_001364992.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC12	ENST00000529221.6	TSL:2 MANE Select	c.1546-62C>T		intron	N/A	ENSP00000433757.1
	TTC12	ENST00000314756.7	TSL:1	c.1546-62C>T		intron	N/A	ENSP00000315160.3
	TTC12	ENST00000494714.5	TSL:1	n.1546-62C>T		intron	N/A	ENSP00000435291.1

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

African (AFR) AF: 0.261 AC: 7270 AN: 27838

American (AMR) AF: 0.216 AC: 7255 AN: 33554

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 3712 AN: 23382

East Asian (EAS) AF: 0.503 AC: 17901 AN: 35568

South Asian (SAS) AF: 0.221 AC: 16250 AN: 73450

European-Finnish (FIN) AF: 0.221 AC: 10861 AN: 49146

Middle Eastern (MID) AF: 0.194 AC: 1019 AN: 5256

European-Non Finnish (NFE) AF: 0.145 AC: 131398 AN: 907108

Other (OTH) AF: 0.190 AC: 9763 AN: 51508

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

African (AFR) AF: 0.265 AC: 10966 AN: 41448

American (AMR) AF: 0.201 AC: 3075 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3468

East Asian (EAS) AF: 0.474 AC: 2436 AN: 5134

South Asian (SAS) AF: 0.228 AC: 1096 AN: 4808

European-Finnish (FIN) AF: 0.230 AC: 2432 AN: 10560

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10043 AN: 67990

Other (OTH) AF: 0.182 AC: 384 AN: 2110

Alfa AF: 0.157 Hom.: 2840

Bravo AF: 0.206

Asia WGS AF: 0.322 AC: 1117 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.44
PhyloP100		-0.64
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: rs2276070; hg19: chr11-113230600; COSMIC: COSV59097892; COSMIC: COSV59097892;