rs953786

Positions:

• chr18-24025823-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001135993.2(TTC39C):​c.167+10785C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,068 control chromosomes in the GnomAD database, including 28,279 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (28279 hom., cov: 31)
• Consequence: TTC39C NM_001135993.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104

Genes affected

TTC39C (HGNC:26595): (tetratricopeptide repeat domain 39C) Predicted to be involved in cilium assembly and otolith morphogenesis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC39C	NM_001135993.2	c.167+10785C>G		intron_variant		ENST00000317571.8	NP_001129465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC39C	ENST00000317571.8	c.167+10785C>G		intron_variant		1	NM_001135993.2	ENSP00000323645	P1
TTC39C	ENST00000304621.10	c.-17+32785C>G		intron_variant		1		ENSP00000306598
TTC39C	ENST00000578150.1	n.126+10785C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83550 AN: 151950 Hom.: 28294 Cov.: 31

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.549 AC: 83524 AN: 152068 Hom.: 28279 Cov.: 31 AF XY: 0.539 AC XY: 40099 AN XY: 74328

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.733

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.699

Gnomad4 NFE AF: 0.777

Gnomad4 OTH AF: 0.584

Alfa AF: 0.647 Hom.: 4410

Bravo AF: 0.524

Asia WGS AF: 0.309 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.2
DANN	Benign	0.75

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: rs953786; hg19: chr18-21605787; COSMIC: COSV58221161;