Variant X-14020459-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001042479.2(GEMIN8):c.91G>T(p.Ala31Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00812 in 1,205,727 control chromosomes in the GnomAD database, including 41 homozygotes. There are 3,075 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 2 hom., 200 hem., cov: 23)

Exomes 𝑓: 0.0083 ( 39 hom. 2875 hem. )

Consequence

GEMIN8
NM_001042479.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.98

Variant links:

Genes affected

GEMIN8 (HGNC:26044): (gem nuclear organelle associated protein 8) The protein encoded by this gene is part of the SMN complex, which is necessary for spliceosomal snRNP assembly in the cytoplasm and pre-mRNA splicing in the nucleus. The encoded protein binds to both SMN1 and the GEMIN6/GEMIN7 heterodimer, mediating their interaction. This protein is found in nuclear Gemini of Cajal bodies (gems) and in the cytoplasm. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, May 2010]

GEMIN8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008584619).

BP6

Variant X-14020459-C-A is Benign according to our data. Variant chrX-14020459-C-A is described in ClinVar as [Benign]. Clinvar id is 719272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-14020459-C-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GEMIN8	NM_001042479.2 linkuse as main transcript	c.91G>T	p.Ala31Ser	missense_variant	4/5	ENST00000680255.1	NP_001035944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GEMIN8	ENST00000680255.1 linkuse as main transcript	c.91G>T	p.Ala31Ser	missense_variant	4/5		NM_001042479.2	ENSP00000505429	P1

Frequencies

GnomAD3 genomes

AF:

0.00609

AC:

682

AN:

112024

Hom.:

Cov.:

AF XY:

0.00585

AC XY:

200

AN XY:

34184

show subpopulations

Gnomad AFR

AF:

0.00107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00160

Gnomad ASJ

AF:

0.00642

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000747

Gnomad FIN

AF:

0.00998

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.00332

GnomAD3 exomes

AF:

0.00597

AC:

1094

AN:

183402

Hom.:

AF XY:

0.00603

AC XY:

409

AN XY:

67850

show subpopulations

Gnomad AFR exome

AF:

0.000760

Gnomad AMR exome

AF:

0.00106

Gnomad ASJ exome

AF:

0.0110

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000681

Gnomad FIN exome

AF:

0.00743

Gnomad NFE exome

AF:

0.0100

Gnomad OTH exome

AF:

0.00486

GnomAD4 exome

AF:

0.00832

AC:

9104

AN:

1093653

Hom.:

Cov.:

AF XY:

0.00800

AC XY:

2875

AN XY:

359173

show subpopulations

Gnomad4 AFR exome

AF:

0.00110

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.00945

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.000611

Gnomad4 FIN exome

AF:

0.00738

Gnomad4 NFE exome

AF:

0.00972

Gnomad4 OTH exome

AF:

0.00753

GnomAD4 genome

AF:

0.00609

AC:

682

AN:

112074

Hom.:

Cov.:

AF XY:

0.00584

AC XY:

200

AN XY:

34244

show subpopulations

Gnomad4 AFR

AF:

0.00107

Gnomad4 AMR

AF:

0.00160

Gnomad4 ASJ

AF:

0.00642

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000750

Gnomad4 FIN

AF:

0.00998

Gnomad4 NFE

AF:

0.0103

Gnomad4 OTH

AF:

0.00328

Alfa

AF:

0.00512

Hom.:

Bravo

AF:

0.00509

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.0118

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.0109

AC:

ExAC

AF:

0.00625

AC:

759

EpiCase

AF:

0.0104

EpiControl

AF:

0.00877

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

T;T;T

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

.;D;D

MetaRNN

Benign

0.0086

T;T;T

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.5

M;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.23

Sift

Uncertain

0.018

D;D;D

Sift4G

Benign

0.081

T;T;T

Polyphen

1.0

D;D;.

Vest4

0.21

MVP

0.38

MPC

0.95

ClinPred

0.016

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.41

gMVP

0.46

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