17-745258-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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:3

Conservation

PhyloP100: 1.21

Publications

50 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

GEMIN4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015721.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GEMIN4	NM_015721.3	MANE Select	c.2785G>A	p.Asp929Asn	missense	Exon 2 of 2	NP_056536.2	P57678

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GEMIN4	ENST00000319004.6	TSL:1 MANE Select	c.2785G>A	p.Asp929Asn	missense	Exon 2 of 2	ENSP00000321706.5	P57678
	GEMIN4	ENST00000576778.1	TSL:6	c.2752G>A	p.Asp918Asn	missense	Exon 1 of 1	ENSP00000459565.1	I3L2C7

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

GnomAD2 exomes

AF:

0.846

AC:

205048

AN:

242470

AF XY:

0.846

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 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

African (AFR)

AF:

0.959

AC:

32072

AN:

33442

American (AMR)

AF:

0.820

AC:

36217

AN:

44166

Ashkenazi Jewish (ASJ)

AF:

0.907

AC:

23615

AN:

26044

East Asian (EAS)

AF:

0.893

AC:

35412

AN:

39640

South Asian (SAS)

AF:

0.866

AC:

74311

AN:

85846

European-Finnish (FIN)

AF:

0.820

AC:

42800

AN:

52198

Middle Eastern (MID)

AF:

0.907

AC:

5234

AN:

5768

European-Non Finnish (NFE)

AF:

0.819

AC:

909822

AN:

1110582

Other (OTH)

AF:

0.859

AC:

51784

AN:

60276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

11645

23291

34936

46582

58227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20962

41924

62886

83848

104810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.866

AC:

131776

AN:

152148

Hom.:

57337

Cov.:

AF XY:

0.866

AC XY:

64434

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.954

AC:

39626

AN:

41532

American (AMR)

AF:

0.848

AC:

12974

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.904

AC:

3137

AN:

3470

East Asian (EAS)

AF:

0.890

AC:

4595

AN:

5162

South Asian (SAS)

AF:

0.874

AC:

4204

AN:

4808

European-Finnish (FIN)

AF:

0.814

AC:

8604

AN:

10574

Middle Eastern (MID)

AF:

0.901

AC:

265

AN:

294

European-Non Finnish (NFE)

AF:

0.821

AC:

55789

AN:

67990

Other (OTH)

AF:

0.884

AC:

1867

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

903

1806

2709

3612

4515

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.840

Hom.:

233621

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.0

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.020

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.20

MetaRNN

Benign

0.0000017

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.76

PhyloP100

1.2

PrimateAI

Benign

0.42

PROVEAN

Benign

0.27

REVEL

Benign

0.089

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.039

MPC

0.13

ClinPred

0.00085

GERP RS

4.7

Varity_R

0.043

gMVP

0.073

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over