NM_001135993.2:c.328A>G

Variant names:

• chr18-24066123-A-G
• rs1489404287
• NM_001135993.2:c.328A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001135993.2(TTC39C):​c.328A>G​(p.Asn110Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000484 in 1,445,108 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: TTC39C NM_001135993.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.82
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28349376).

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.328A>G	p.Asn110Asp	missense	Exon 3 of 14	NP_001129465.1	Q8N584-1
	TTC39C	NM_153211.4		c.145A>G	p.Asn49Asp	missense	Exon 3 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.328A>G	p.Asn110Asp	missense	Exon 3 of 14	ENSP00000323645.3	Q8N584-1
	TTC39C	ENST00000304621.10	TSL:1	c.145A>G	p.Asn49Asp	missense	Exon 3 of 14	ENSP00000306598.6	Q8N584-2
	TTC39C	ENST00000919100.1		c.328A>G	p.Asn110Asp	missense	Exon 3 of 14	ENSP00000589159.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000484 AC: 7 AN: 1445108 Hom.: 0 Cov.: 31 AF XY: 0.00000417 AC XY: 3 AN XY: 718622

African (AFR) AF: 0.00 AC: 0 AN: 32240

American (AMR) AF: 0.00 AC: 0 AN: 39186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25672

East Asian (EAS) AF: 0.00 AC: 0 AN: 39082

South Asian (SAS) AF: 0.00 AC: 0 AN: 82128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00000632 AC: 7 AN: 1108064

Other (OTH) AF: 0.00 AC: 0 AN: 59760

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	0.32
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		8.8
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.21
Sift	Benign	0.048	D
Sift4G	Benign	0.094	T
Polyphen		0.83	P
Vest4		0.29
MutPred		0.47		Loss of MoRF binding (P = 0.0568)
MVP		0.53
MPC		0.95
ClinPred		0.88	D
GERP RS		5.4
Varity_R		0.34
gMVP		0.48
Mutation Taster		=52/48	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: rs1489404287; hg19: chr18-21646087;