1-51290008-G-C

Position:

• chr1-51290008-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001297663.2(TTC39A):​c.1490C>G​(p.Ala497Gly) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTC39A NM_001297663.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.04

Genes affected

TTC39A (HGNC:18657): (tetratricopeptide repeat domain 39A) Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

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=0.21066996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC39A	NM_001297663.2	c.1490C>G	p.Ala497Gly	missense_variant	16/18	ENST00000680483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC39A	ENST00000680483.1	c.1490C>G	p.Ala497Gly	missense_variant	16/18		NM_001297663.2	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Wolff-Parkinson-White pattern Uncertain:1

Uncertain significance, no assertion criteria provided

research

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Jul 14, 2017

This variant was identified in an individual with Wolff-Parkinson-White syndrome -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Benign	0.90
Eigen	Benign	-0.096
Eigen_PC	Benign	0.050
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.76	T;T;T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.21	T;T;T;T;T
MetaSVM	Benign	-0.80	T
MutationTaster	Benign	0.86	D;D;D;D;D;D
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.7	N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.29	T;T;T;T;T
Sift4G	Benign	0.46	T;T;T;T;T
Polyphen		0.0010, 0.0020, 0.0	.;B;B;B;.
Vest4		0.25
MutPred		0.34		.;Loss of helix (P = 0.0444);.;.;.;
MVP		0.54
MPC		0.37
ClinPred		0.27	T
GERP RS		6.1
Varity_R		0.088
gMVP		0.078

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1553171591; hg19: chr1-51755680;