chr18-24082990-A-T

Position:

• chr18-24082990-A-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.893A>T​(p.Asp298Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTC39C NM_001135993.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.17

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]

ENSG00000265204 (HGNC:):

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=0.2223241).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC39C	NM_001135993.2	c.893A>T	p.Asp298Val	missense_variant	6/14	ENST00000317571.8	NP_001129465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC39C	ENST00000317571.8	c.893A>T	p.Asp298Val	missense_variant	6/14	1	NM_001135993.2	ENSP00000323645.3
TTC39C	ENST00000304621.10	c.710A>T	p.Asp237Val	missense_variant	6/14	1		ENSP00000306598.6
ENSG00000265204	ENST00000578443.1	n.99-5731T>A		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 14, 2023

The c.893A>T (p.D298V) alteration is located in exon 6 (coding exon 6) of the TTC39C gene. This alteration results from a A to T substitution at nucleotide position 893, causing the aspartic acid (D) at amino acid position 298 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.0029	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	20
DANN	Uncertain	0.97
DEOGEN2	Benign	0.028	.;T
Eigen	Benign	-0.25
Eigen_PC	Benign	0.0075
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.34	.;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.70	N;N
REVEL	Benign	0.27
Sift	Benign	0.28	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.0030	.;B
Vest4		0.47
MutPred		0.46		.;Loss of disorder (P = 0.0069);
MVP		0.53
MPC		0.69
ClinPred		0.54	D
GERP RS		5.7
Varity_R		0.21
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-21662954;