Variant 17-745258-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015721.3(GEMIN4):c.2785G>A(p.Asp929Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 1,610,110 control chromosomes in the GnomAD database, including 561,509 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 57337 hom., cov: 31)

Exomes 𝑓: 0.83 ( 504172 hom. )

Consequence

GEMIN4
NM_015721.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.21

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.6844264E-6).

BP6

Variant 17-745258-C-T is Benign according to our data. Variant chr17-745258-C-T is described in ClinVar as [Benign]. Clinvar id is 1185306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GEMIN4	NM_015721.3 linkuse as main transcript	c.2785G>A	p.Asp929Asn	missense_variant	2/2	ENST00000319004.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GEMIN4	ENST00000319004.6 linkuse as main transcript	c.2785G>A	p.Asp929Asn	missense_variant	2/2	1	NM_015721.3	P1
GEMIN4	ENST00000576778.1 linkuse as main transcript	c.2752G>A	p.Asp918Asn	missense_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.866

AC:

131653

AN:

152030

Hom.:

57275

Cov.:

show subpopulations

Gnomad AFR

AF:

0.954

Gnomad AMI

AF:

0.786

Gnomad AMR

AF:

0.848

Gnomad ASJ

AF:

0.904

Gnomad EAS

AF:

0.890

Gnomad SAS

AF:

0.875

Gnomad FIN

AF:

0.814

Gnomad MID

AF:

0.896

Gnomad NFE

AF:

0.821

Gnomad OTH

AF:

0.882

GnomAD3 exomes

AF:

0.846

AC:

205048

AN:

242470

Hom.:

86940

AF XY:

0.846

AC XY:

111789

AN XY:

132084

show subpopulations

Gnomad AFR exome

AF:

0.957

Gnomad AMR exome

AF:

0.813

Gnomad ASJ exome

AF:

0.908

Gnomad EAS exome

AF:

0.884

Gnomad SAS exome

AF:

0.868

Gnomad FIN exome

AF:

0.819

Gnomad NFE exome

AF:

0.827

Gnomad OTH exome

AF:

0.859

GnomAD4 exome

AF:

0.831

AC:

1211267

AN:

1457962

Hom.:

504172

Cov.:

AF XY:

0.832

AC XY:

602897

AN XY:

725036

show subpopulations

Gnomad4 AFR exome

AF:

0.959

Gnomad4 AMR exome

AF:

0.820

Gnomad4 ASJ exome

AF:

0.907

Gnomad4 EAS exome

AF:

0.893

Gnomad4 SAS exome

AF:

0.866

Gnomad4 FIN exome

AF:

0.820

Gnomad4 NFE exome

AF:

0.819

Gnomad4 OTH exome

AF:

0.859

GnomAD4 genome

AF:

0.866

AC:

131776

AN:

152148

Hom.:

57337

Cov.:

AF XY:

0.866

AC XY:

64434

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.954

Gnomad4 AMR

AF:

0.848

Gnomad4 ASJ

AF:

0.904

Gnomad4 EAS

AF:

0.890

Gnomad4 SAS

AF:

0.874

Gnomad4 FIN

AF:

0.814

Gnomad4 NFE

AF:

0.821

Gnomad4 OTH

AF:

0.884

Alfa

AF:

0.839

Hom.:

129787

Bravo

AF:

0.874

TwinsUK

AF:

0.815

AC:

3022

ALSPAC

AF:

0.821

AC:

3164

ESP6500AA

AF:

0.955

AC:

3673

ESP6500EA

AF:

0.826

AC:

6829

ExAC

AF:

0.843

AC:

101807

Asia WGS

AF:

0.905

AC:

3146

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 03, 2020

This variant is associated with the following publications: (PMID: 21118967) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.0

DANN

Benign

0.79

DEOGEN2

Benign

0.020

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.20

T;T

MetaRNN

Benign

0.0000017

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.76

N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.42

PROVEAN

Benign

0.27

N;.

REVEL

Benign

0.089

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.039

MPC

0.13

ClinPred

0.00085

GERP RS

4.7

Varity_R

0.043

gMVP

0.073

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