chr1-51302516-C-T

Position:

• chr1-51302516-C-T

Variant summary

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

The NM_001297663.2(TTC39A):​c.821G>A​(p.Arg274Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000686 in 1,457,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R274W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: TTC39A NM_001297663.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

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=0.197725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC39A	NM_001297663.2	c.821G>A	p.Arg274Gln	missense_variant	10/18	ENST00000680483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC39A	ENST00000680483.1	c.821G>A	p.Arg274Gln	missense_variant	10/18		NM_001297663.2	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000832 AC: 2 AN: 240522 Hom.: 0 AF XY: 0.0000154 AC XY: 2 AN XY: 130278

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000343

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000918

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000686 AC: 10 AN: 1457380 Hom.: 0 Cov.: 34 AF XY: 0.00000690 AC XY: 5 AN XY: 724426

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.0000498

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000248 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T;.;.;.;T;.;.;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.088
FATHMM_MKL	Benign	0.29	N
LIST_S2	Uncertain	0.91	D;D;D;D;D;D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.20	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.7	L;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.2	N;N;N;N;N;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.40	T;T;T;T;T;T;T;T
Sift4G	Benign	0.15	T;T;T;T;T;T;.;T
Polyphen		0.67	P;B;B;.;.;D;.;.
Vest4		0.34
MutPred		0.56		Gain of ubiquitination at K313 (P = 0.0797);.;.;.;.;.;.;.;
MVP		0.40
MPC		0.95
ClinPred		0.75	D
GERP RS		5.2
Varity_R		0.18
gMVP		0.27

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

LitVar

Other links and lift over

dbSNP: rs765718230; hg19: chr1-51768188;