20-45375493-C-T

Position:

chr20-45375493-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014477.3(TP53TG5):c.314G>A(p.Cys105Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,609,298 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 (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

TP53TG5
NM_014477.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0200

Variant links:

Genes affected

TP53TG5 (HGNC:15856): (TP53 target 5) Located in chromosome and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

TP53TG5 links:

SYS1-DBNDD2 (HGNC:33535): (SYS1-DBNDD2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription from the neighboring SYS1 Golgi-localized integral membrane protein homolog and dysbindin domain containing 2 (DBNDD2) genes. The read-through transcript includes the majority of exons from each individual gene, but it would be subject to nonsense-mediated mRNA decay (NMD) and is therefore predicted to be non-coding. [provided by RefSeq, Oct 2010]

SYS1-DBNDD2 links:

SYS1 (HGNC:16162): (SYS1 golgi trafficking protein) SYS1 forms a complex with ADP-ribosylation factor-related protein ARFRP1 (MIM 604699) and targets ARFRP1 to the Golgi apparatus (Behnia et al., 2004 [PubMed 15077113]).[supplied by OMIM, Aug 2009]

SYS1 links:

TP53TG5 (HGNC:):

TP53TG5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043573022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP53TG5	NM_014477.3 linkuse as main transcript	c.314G>A	p.Cys105Tyr	missense_variant	4/5	ENST00000372726.5	NP_055292.1
TP53TG5	XM_011528790.3 linkuse as main transcript	c.266G>A	p.Cys89Tyr	missense_variant	4/5		XP_011527092.1
SYS1	NM_001099791.3 linkuse as main transcript	c.*1199C>T		3_prime_UTR_variant	4/4		NP_001093261.1	Q8N2H4-2
SYS1-DBNDD2	NR_003189.2 linkuse as main transcript	n.380+9807C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP53TG5	ENST00000372726.5 linkuse as main transcript	c.314G>A	p.Cys105Tyr	missense_variant	4/5	1	NM_014477.3	ENSP00000361811.3		Q9Y2B4
SYS1-DBNDD2	ENST00000458187.5 linkuse as main transcript	n.230+9807C>T		intron_variant		5		ENSP00000457768.1		H3BUS1

Frequencies

GnomAD3 genomes

AF:

0.000135

AC:

AN:

147718

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000464

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00331

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

250566

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135612

show subpopulations

Gnomad AFR exome

AF:

0.000372

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461460

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727060

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000135

AC:

AN:

147838

Hom.:

Cov.:

AF XY:

0.000153

AC XY:

AN XY:

71876

show subpopulations

Gnomad4 AFR

AF:

0.000462

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000128

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 13, 2024

The c.314G>A (p.C105Y) alteration is located in exon 4 (coding exon 4) of the TP53TG5 gene. This alteration results from a G to A substitution at nucleotide position 314, causing the cysteine (C) at amino acid position 105 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.59

CADD

Benign

9.7

DANN

Benign

0.76

DEOGEN2

Benign

0.016

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.38

M_CAP

Benign

0.0050

MetaRNN

Benign

0.044

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.030

Sift

Uncertain

0.0090

Sift4G

Benign

0.29

Polyphen

0.86

Vest4

0.24

MVP

0.030

MPC

0.51

ClinPred

0.15

GERP RS

-0.71

Varity_R

0.23

gMVP

0.025

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over