18-24102336-C-T

Variant names:

• chr18-24102336-C-T
• rs16940484
• NM_001135993.2:c.985-12218C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001135993.2(TTC39C):​c.985-12218C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,068 control chromosomes in the GnomAD database, including 5,449 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 0.24 (5449 hom., cov: 33)
• Consequence: TTC39C NM_001135993.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 7 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135993.2. 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
	TTC39C	NM_001135993.2	MANE Select	c.985-12218C>T		intron	N/A	NP_001129465.1	Q8N584-1
	TTC39C	NM_153211.4		c.802-12218C>T		intron	N/A	NP_694943.2	Q8N584-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC39C	ENST00000317571.8	TSL:1 MANE Select	c.985-12218C>T		intron	N/A	ENSP00000323645.3	Q8N584-1
	TTC39C	ENST00000304621.10	TSL:1	c.802-12218C>T		intron	N/A	ENSP00000306598.6	Q8N584-2
	TTC39C	ENST00000919100.1		c.985-12218C>T		intron	N/A	ENSP00000589159.1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35834 AN: 151950 Hom.: 5442 Cov.: 33

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.236 AC: 35890 AN: 152068 Hom.: 5449 Cov.: 33 AF XY: 0.238 AC XY: 17665 AN XY: 74352

African (AFR) AF: 0.412 AC: 17072 AN: 41422

American (AMR) AF: 0.194 AC: 2969 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 850 AN: 3468

East Asian (EAS) AF: 0.315 AC: 1629 AN: 5174

South Asian (SAS) AF: 0.266 AC: 1282 AN: 4828

European-Finnish (FIN) AF: 0.142 AC: 1507 AN: 10576

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9729 AN: 68000

Other (OTH) AF: 0.230 AC: 485 AN: 2110

Alfa AF: 0.123 Hom.: 384

Bravo AF: 0.245

Asia WGS AF: 0.254 AC: 881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.46
DANN	Benign	0.82
PhyloP100		-1.5
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: rs16940484; hg19: chr18-21682300;