18-24014882-C-G

Variant names:

• chr18-24014882-C-G
• rs1461385169
• NM_001135993.2:c.11C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001135993.2(TTC39C):​c.11C>G​(p.Ser4Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 151,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S4L) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: TTC39C NM_001135993.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.15
• Publications: 0 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]

TTC39C-AS1 (HGNC:51321): (TTC39C antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23324373).

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.11C>G	p.Ser4Trp	missense	Exon 1 of 14	NP_001129465.1	Q8N584-1
	TTC39C	NM_001243425.2		c.11C>G	p.Ser4Trp	missense	Exon 1 of 2	NP_001230354.1	Q8N584-3
	TTC39C	NM_153211.4		c.-17+21844C>G		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.11C>G	p.Ser4Trp	missense	Exon 1 of 14	ENSP00000323645.3	Q8N584-1
	TTC39C	ENST00000584250.2	TSL:1	c.11C>G	p.Ser4Trp	missense	Exon 1 of 2	ENSP00000464344.1	Q8N584-3
	TTC39C	ENST00000304621.10	TSL:1	c.-17+21844C>G		intron	N/A	ENSP00000306598.6	Q8N584-2

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151594 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151594 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74030

African (AFR) AF: 0.00 AC: 0 AN: 41336

American (AMR) AF: 0.00 AC: 0 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10470

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67840

Other (OTH) AF: 0.00 AC: 0 AN: 2076

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Pathogenic	29
DANN	Benign	0.94
DEOGEN2	Benign	0.037	T
Eigen	Benign	0.0033
Eigen_PC	Benign	0.074
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.74	T
M_CAP	Pathogenic	0.53	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.1
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.053
Sift	Uncertain	0.015	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.96	D
Vest4		0.23
MutPred		0.21		Loss of phosphorylation at S4 (P = 0.0157)
MVP		0.32
MPC		0.73
ClinPred		0.69	D
GERP RS		3.6
PromoterAI		-0.013	Neutral
Varity_R		0.13
gMVP		0.51

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: rs1461385169; hg19: chr18-21594846;