rs2029238

Positions:

• chr18-24122142-G-A
• chr18-24122142-G-C
• chr18-24122142-G-T

Variant summary

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

The NM_001135993.2(TTC39C):​c.1187-1692G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,004 control chromosomes in the GnomAD database, including 1,288 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 0.12 (1288 hom., cov: 31)
• Consequence: TTC39C NM_001135993.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC39C	NM_001135993.2	c.1187-1692G>A		intron_variant		ENST00000317571.8	NP_001129465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC39C	ENST00000317571.8	c.1187-1692G>A		intron_variant		1	NM_001135993.2	ENSP00000323645	P1
TTC39C	ENST00000304621.10	c.1004-1692G>A		intron_variant		1		ENSP00000306598
TTC39C	ENST00000540918.2	c.266-1692G>A		intron_variant		2		ENSP00000443016
TTC39C	ENST00000579214.1	c.98-1692G>A		intron_variant		2		ENSP00000463283

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18456 AN: 151886 Hom.: 1289 Cov.: 31

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.00367

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.121 AC: 18467 AN: 152004 Hom.: 1288 Cov.: 31 AF XY: 0.122 AC XY: 9074 AN XY: 74274

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.00368

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.139

Alfa AF: 0.117 Hom.: 620

Bravo AF: 0.116

Asia WGS AF: 0.0860 AC: 299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.58

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: rs2029238; hg19: chr18-21702106;