Variant 16-85634010-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014615.5(GSE1):c.104A>G(p.Asn35Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000313 in 1,612,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

GSE1
NM_014615.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.42

Variant links:

Genes affected

GSE1 (HGNC:28979): (Gse1 coiled-coil protein) This gene encodes a proline-rich protein with coiled coil domains that may be a subunit of a BRAF35-HDAC (BHC) histone deacetylase complex. This gene may function as an oncogene in breast cancer and enhanced expression of the encoded protein has been observed in breast cancer patients. [provided by RefSeq, May 2017]

GSE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.14169979).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSE1	NM_014615.5 linkuse as main transcript	c.104A>G	p.Asn35Ser	missense_variant	2/16	ENST00000253458.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSE1	ENST00000253458.12 linkuse as main transcript	c.104A>G	p.Asn35Ser	missense_variant	2/16	5	NM_014615.5	A2	Q14687-1

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

151936

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000270

AC:

AN:

247836

Hom.:

AF XY:

0.000282

AC XY:

AN XY:

134588

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000204

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.000459

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000319

AC:

466

AN:

1460068

Hom.:

Cov.:

AF XY:

0.000326

AC XY:

237

AN XY:

726374

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000133

Gnomad4 NFE exome

AF:

0.000384

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000250

AC:

AN:

151936

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

AN XY:

74210

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.000389

Hom.:

Bravo

AF:

0.000242

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000239

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000653

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

Aug 13, 2021

The c.104A>G (p.N35S) alteration is located in exon 2 (coding exon 2) of the GSE1 gene. This alteration results from a A to G substitution at nucleotide position 104, causing the asparagine (N) at amino acid position 35 to be replaced by a serine (S). 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

0.096

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.018

T;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.035

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.75

Polyphen

0.99

.;D

Vest4

0.67

MVP

0.47

ClinPred

0.098

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.16

gMVP

0.42

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