chr11-113324873-A-G

Position:

• chr11-113324873-A-G

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.322+191A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 151,972 control chromosomes in the GnomAD database, including 29,678 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.62 (29678 hom., cov: 31)
• Consequence: TTC12 NM_017868.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.960

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=-0.91).
• BP6: Variant 11-113324873-A-G is Benign according to our data. Variant chr11-113324873-A-G is described in ClinVar as [Benign]. Clinvar id is 1244086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC12	NM_017868.4	c.322+191A>G		intron_variant		ENST00000529221.6	NP_060338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC12	ENST00000529221.6	c.322+191A>G		intron_variant		2	NM_017868.4	ENSP00000433757	A2

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94550 AN: 151854 Hom.: 29665 Cov.: 31

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.623 AC: 94606 AN: 151972 Hom.: 29678 Cov.: 31 AF XY: 0.616 AC XY: 45788 AN XY: 74296

Gnomad4 AFR AF: 0.618

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.643

Gnomad4 OTH AF: 0.628

Alfa AF: 0.640 Hom.: 41848

Bravo AF: 0.629

Asia WGS AF: 0.615 AC: 2139 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 15, 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	-0.91
CADD	Benign	0.31
DANN	Benign	0.61

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: rs948178; hg19: chr11-113195595;