Variant chr22-46308713-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_016426.7(GTSE1):c.532G>T(p.Val178Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00266 in 1,613,696 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 46 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 45 hom. )

Consequence

GTSE1
NM_016426.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.35

Variant links:

Genes affected

GTSE1 (HGNC:13698): (G2 and S-phase expressed 1) The protein encoded by this gene is only expressed in the S and G2 phases of the cell cycle, where it colocalizes with cytoplasmic tubulin and microtubules. In response to DNA damage, the encoded protein accumulates in the nucleus and binds the tumor suppressor protein p53, shuttling it out of the nucleus and repressing its ability to induce apoptosis. [provided by RefSeq, Jul 2008]

GTSE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022632778).

BP6

Variant 22-46308713-G-T is Benign according to our data. Variant chr22-46308713-G-T is described in ClinVar as [Benign]. Clinvar id is 777737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0144 (2201/152384) while in subpopulation AFR AF= 0.0498 (2072/41594). AF 95% confidence interval is 0.048. There are 46 homozygotes in gnomad4. There are 1084 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTSE1	NM_016426.7 link	c.532G>T	p.Val178Leu	missense_variant	Exon 4 of 12	ENST00000454366.2	NP_057510.5	Q9NYZ3
GTSE1	XM_047441391.1 link	c.532G>T	p.Val178Leu	missense_variant	Exon 3 of 11		XP_047297347.1
GTSE1	XM_047441392.1 link	c.532G>T	p.Val178Leu	missense_variant	Exon 4 of 10		XP_047297348.1
GTSE1	XR_007067974.1 link	n.615G>T		non_coding_transcript_exon_variant	Exon 4 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTSE1	ENST00000454366.2 link	c.532G>T	p.Val178Leu	missense_variant	Exon 4 of 12	1	NM_016426.7	ENSP00000415430.1		Q9NYZ3

Frequencies

GnomAD3 genomes

AF:

0.0144

AC:

2194

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0498

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00615

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00907

GnomAD3 exomes

AF:

0.00372

AC:

925

AN:

248786

Hom.:

AF XY:

0.00289

AC XY:

390

AN XY:

135066

show subpopulations

Gnomad AFR exome

AF:

0.0507

Gnomad AMR exome

AF:

0.00206

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000206

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00143

AC:

2089

AN:

1461312

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

907

AN XY:

726924

show subpopulations

Gnomad4 AFR exome

AF:

0.0493

Gnomad4 AMR exome

AF:

0.00273

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000638

Gnomad4 OTH exome

AF:

0.00351

GnomAD4 genome

AF:

0.0144

AC:

2201

AN:

152384

Hom.:

Cov.:

AF XY:

0.0145

AC XY:

1084

AN XY:

74528

show subpopulations

Gnomad4 AFR

AF:

0.0498

Gnomad4 AMR

AF:

0.00614

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00898

Alfa

AF:

0.000785

Hom.:

Bravo

AF:

0.0164

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0433

AC:

190

ESP6500EA

AF:

0.000234

AC:

ExAC

AF:

0.00456

AC:

553

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 17, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.0090

DANN

Benign

0.35

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0049

MetaRNN

Benign

0.0023

MetaSVM

Benign

-0.95

PrimateAI

Benign

0.31

PROVEAN

Benign

0.050

REVEL

Benign

0.0030

Sift

Benign

0.84

Sift4G

Benign

0.91

Vest4

0.028

MVP

0.014

MPC

0.14

ClinPred

0.0025

GERP RS

-8.9

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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