rs953786

Variant names:

• chr18-24025823-C-G
• rs953786
• NM_001135993.2:c.167+10785C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TTC39C	NM_001135993.2	c.167+10785C>G		intron_variant	Intron 1 of 13	ENST00000317571.8	NP_001129465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC39C	ENST00000317571.8	c.167+10785C>G		intron_variant	Intron 1 of 13	1	NM_001135993.2	ENSP00000323645.3
TTC39C	ENST00000304621.10	c.-17+32785C>G		intron_variant	Intron 1 of 13	1		ENSP00000306598.6
TTC39C	ENST00000578150.1	n.126+10785C>G		intron_variant	Intron 1 of 3	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

African (AFR) AF: 0.177 AC: 7337 AN: 41474

American (AMR) AF: 0.521 AC: 7974 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2542 AN: 3470

East Asian (EAS) AF: 0.287 AC: 1482 AN: 5164

South Asian (SAS) AF: 0.398 AC: 1919 AN: 4822

European-Finnish (FIN) AF: 0.699 AC: 7371 AN: 10550

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.777 AC: 52805 AN: 67976

Other (OTH) AF: 0.584 AC: 1233 AN: 2110

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
PhyloP100		-0.10
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: rs953786; hg19: chr18-21605787; COSMIC: COSV58221161;