rs1461385169

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr18-24014882-C-G
• chr18-24014882-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC39C	NM_001135993.2	c.11C>G	p.Ser4Trp	missense_variant	Exon 1 of 14	ENST00000317571.8	NP_001129465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC39C	ENST00000317571.8	c.11C>G	p.Ser4Trp	missense_variant	Exon 1 of 14	1	NM_001135993.2	ENSP00000323645.3

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

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Pathogenic	0.53	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.5	.;N
REVEL	Benign	0.053
Sift	Uncertain	0.015	.;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.96	.;D
Vest4		0.23
MutPred		0.21		Loss of phosphorylation at S4 (P = 0.0157);Loss of phosphorylation at S4 (P = 0.0157);
MVP		0.32
MPC		0.73
ClinPred		0.69	D
GERP RS		3.6
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

Publications

LitVar

Other links and lift over

dbSNP: rs1461385169; hg19: chr18-21594846;