rs719804

Variant names:

• chr11-113364053-A-G
• rs719804
• NM_017868.4:c.1816+126A>G

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+126A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 633,980 control chromosomes in the GnomAD database, including 16,576 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3665 hom., cov: 33)
  • Exomes 𝑓: 0.23 (12911 hom.)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.724
• Publications: 8 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: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics
• 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=-0.92).
• BP6: Variant 11-113364053-A-G is Benign according to our data. Variant chr11-113364053-A-G is described in ClinVar as Benign. ClinVar VariationId is 1275576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.241 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.1816+126A>G		intron	N/A	NP_060338.3
	TTC12	NM_001318533.2		c.1834+126A>G		intron	N/A	NP_001305462.1	J3KR69
	TTC12	NM_001378063.1		c.1819+126A>G		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.1816+126A>G		intron	N/A	ENSP00000433757.1	Q9H892-1
	TTC12	ENST00000314756.7	TSL:1	c.1816+126A>G		intron	N/A	ENSP00000315160.3	Q9H892-2
	TTC12	ENST00000494714.5	TSL:1	n.1816+126A>G		intron	N/A	ENSP00000435291.1	Q9H892-2

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32890 AN: 152152 Hom.: 3665 Cov.: 33

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.212

GnomAD4 exome AF: 0.225 AC: 108512 AN: 481710 Hom.: 12911 AF XY: 0.228 AC XY: 58140 AN XY: 254720

African (AFR) AF: 0.213 AC: 2651 AN: 12462

American (AMR) AF: 0.135 AC: 2441 AN: 18108

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 3288 AN: 13998

East Asian (EAS) AF: 0.104 AC: 3131 AN: 30012

South Asian (SAS) AF: 0.244 AC: 11102 AN: 45572

European-Finnish (FIN) AF: 0.180 AC: 6782 AN: 37700

Middle Eastern (MID) AF: 0.223 AC: 810 AN: 3634

European-Non Finnish (NFE) AF: 0.247 AC: 72272 AN: 293132

Other (OTH) AF: 0.223 AC: 6035 AN: 27092

GnomAD4 genome AF: 0.216 AC: 32923 AN: 152270 Hom.: 3665 Cov.: 33 AF XY: 0.212 AC XY: 15782 AN XY: 74470

African (AFR) AF: 0.207 AC: 8581 AN: 41538

American (AMR) AF: 0.168 AC: 2569 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 841 AN: 3468

East Asian (EAS) AF: 0.106 AC: 548 AN: 5182

South Asian (SAS) AF: 0.253 AC: 1221 AN: 4834

European-Finnish (FIN) AF: 0.171 AC: 1809 AN: 10606

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.244 AC: 16577 AN: 68016

Other (OTH) AF: 0.213 AC: 451 AN: 2114

Alfa AF: 0.233 Hom.: 7002

Bravo AF: 0.213

Asia WGS AF: 0.180 AC: 628 AN: 3478

ClinVar

ClinVar submissions

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	-0.92
CADD	Benign	0.74
DANN	Benign	0.64
PhyloP100		-0.72
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: rs719804; hg19: chr11-113234775;