1-51321821-G-A

Position:

• chr1-51321821-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001297663.2(TTC39A):​c.46C>T​(p.Pro16Ser) 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTC39A NM_001297663.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.490

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04239577).
• BP6: Variant 1-51321821-G-A is Benign according to our data. Variant chr1-51321821-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2612201.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC39A	NM_001297663.2	c.46C>T	p.Pro16Ser	missense_variant	2/18	ENST00000680483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC39A	ENST00000680483.1	c.46C>T	p.Pro16Ser	missense_variant	2/18		NM_001297663.2	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.7
DANN	Benign	0.33
DEOGEN2	Benign	0.0066	T;.;.;T;.;.;T;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.77	T;T;T;T;T;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.042	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.28	N;.;N;.;.;.;.;.
MutationTaster	Benign	1.0	D;N;N;N;N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.080	N;N;N;N;N;N;N;N
REVEL	Benign	0.016
Sift	Benign	0.71	T;T;T;T;T;T;T;T
Sift4G	Benign	0.81	T;T;T;T;T;T;T;T
Polyphen		0.0	B;B;.;.;B;.;.;.
Vest4		0.044
MutPred		0.17		Gain of catalytic residue at P17 (P = 0.0319);.;Gain of catalytic residue at P17 (P = 0.0319);.;.;.;.;.;
MVP		0.092
MPC		0.37
ClinPred		0.022	T
GERP RS		0.049
Varity_R		0.026
gMVP		0.12

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: rs755415096; hg19: chr1-51787493;