Variant 17-745069-T-C 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 ENST00000319004.6(GEMIN4):c.2974A>G(p.Met992Val) variant causes a missense change. The variant allele was found at a frequency of 0.000559 in 1,613,690 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 2 hom. )

Consequence

GEMIN4
ENST00000319004.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.16

Variant links:

Genes affected

GEMIN4 (HGNC:15717): (gem nuclear organelle associated protein 4) The product of this gene is part of a large complex localized to the cytoplasm, nucleoli, and to discrete nuclear bodies called Gemini bodies (gems). The complex functions in spliceosomal snRNP assembly in the cytoplasm, and regenerates spliceosomes required for pre-mRNA splicing in the nucleus. The encoded protein directly interacts with a DEAD box protein and several spliceosome core proteins. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

GEMIN4 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=0.011332035).

BP6

Variant 17-745069-T-C is Benign according to our data. Variant chr17-745069-T-C is described in ClinVar as [Benign]. Clinvar id is 734199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GEMIN4	NM_015721.3 linkuse as main transcript	c.2974A>G	p.Met992Val	missense_variant	2/2	ENST00000319004.6	NP_056536.2	P57678Q8WUM5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GEMIN4	ENST00000319004.6 linkuse as main transcript	c.2974A>G	p.Met992Val	missense_variant	2/2	1	NM_015721.3	ENSP00000321706.5		P57678
GEMIN4	ENST00000576778.1 linkuse as main transcript	c.2941A>G	p.Met981Val	missense_variant	1/1	6		ENSP00000459565.1		I3L2C7

Frequencies

GnomAD3 genomes

AF:

0.00310

AC:

472

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.000834

AC:

207

AN:

248348

Hom.:

AF XY:

0.000593

AC XY:

AN XY:

134866

show subpopulations

Gnomad AFR exome

AF:

0.0111

Gnomad AMR exome

AF:

0.000784

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000267

Gnomad OTH exome

AF:

0.000663

GnomAD4 exome

AF:

0.000294

AC:

430

AN:

1461412

Hom.:

Cov.:

AF XY:

0.000239

AC XY:

174

AN XY:

726974

show subpopulations

Gnomad4 AFR exome

AF:

0.0103

Gnomad4 AMR exome

AF:

0.000739

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.000613

GnomAD4 genome

AF:

0.00310

AC:

472

AN:

152278

Hom.:

Cov.:

AF XY:

0.00283

AC XY:

211

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0107

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.000742

Hom.:

Bravo

AF:

0.00336

ESP6500AA

AF:

0.00857

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.000802

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	GEMIN4: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

T;.

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.77

T;T

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.1

D;.

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.99

D;.

Vest4

0.77

MVP

0.67

MPC

0.60

ClinPred

0.031

GERP RS

5.8

Varity_R

0.72

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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