rs977845100

Variant names:

• chr18-24069188-T-C
• rs977845100
• NM_001135993.2:c.377T>C

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.377T>C​(p.Val126Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 7.63
• 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]

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=0.1919389).

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.377T>C	p.Val126Ala	missense	Exon 4 of 14	NP_001129465.1	Q8N584-1
	TTC39C	NM_153211.4		c.194T>C	p.Val65Ala	missense	Exon 4 of 14	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.377T>C	p.Val126Ala	missense	Exon 4 of 14	ENSP00000323645.3	Q8N584-1
	TTC39C	ENST00000304621.10	TSL:1	c.194T>C	p.Val65Ala	missense	Exon 4 of 14	ENSP00000306598.6	Q8N584-2
	TTC39C	ENST00000919100.1		c.377T>C	p.Val126Ala	missense	Exon 4 of 14	ENSP00000589159.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.018	T
Eigen	Benign	0.020
Eigen_PC	Benign	0.22
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		7.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.13
Sift	Benign	0.41	T
Sift4G	Benign	0.81	T
Polyphen		0.0050	B
Vest4		0.30
MutPred		0.58		Gain of disorder (P = 0.0396)
MVP		0.38
MPC		0.59
ClinPred		0.80	D
GERP RS		5.5
Varity_R		0.072
gMVP		0.25
Mutation Taster		=60/40	polymorphism

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: rs977845100; hg19: chr18-21649152;