1-51288188-C-T

Position:

• chr1-51288188-C-T

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.1703G>A​(p.Ser568Asn) 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: -1.11

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=0.03103906).
• BP6: Variant 1-51288188-C-T is Benign according to our data. Variant chr1-51288188-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2292836.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC39A	NM_001297663.2	c.1703G>A	p.Ser568Asn	missense_variant	18/18	ENST00000680483.1	NP_001284592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC39A	ENST00000680483.1	c.1703G>A	p.Ser568Asn	missense_variant	18/18		NM_001297663.2	ENSP00000505859	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

May 27, 2022

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	0.071
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.015
DANN	Benign	0.41
DEOGEN2	Benign	0.010	.;T;.;.;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.16	T;T;T;T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.031	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	.;L;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.40	N;N;N;N;N
REVEL	Benign	0.050
Sift	Benign	0.40	T;T;T;T;T
Sift4G	Benign	0.34	T;T;T;T;T
Polyphen		0.0	.;B;B;B;.
Vest4		0.044
MutPred		0.15		.;Loss of phosphorylation at S604 (P = 0.0145);.;.;.;
MVP		0.088
MPC		0.34
ClinPred		0.085	T
GERP RS		-11
Varity_R		0.034
gMVP		0.18

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: chr1-51753860;