rs2740348

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1348C>G(p.Gln450Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 1,613,310 control chromosomes in the GnomAD database, including 563,156 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 ( 57341 hom., cov: 30)

Exomes 𝑓: 0.83 ( 505815 hom. )

Consequence

GEMIN4
NM_015721.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.23

Publications

73 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=7.732567E-7).

BP6

Variant 17-746695-G-C is Benign according to our data. Variant chr17-746695-G-C is described in ClinVar as Benign. ClinVar VariationId is 1185310.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 rank	MANE	Protein	UniProt
GEMIN4	NM_015721.3 link	c.1348C>G	p.Gln450Glu	missense_variant	Exon 2 of 2	ENST00000319004.6	NP_056536.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
GEMIN4	ENST00000319004.6 link	c.1348C>G	p.Gln450Glu	missense_variant	Exon 2 of 2	1	NM_015721.3	ENSP00000321706.5
GEMIN4	ENST00000576778.1 link	c.1315C>G	p.Gln439Glu	missense_variant	Exon 1 of 1	6		ENSP00000459565.1
GEMIN4	ENST00000437269.1 link	c.*531C>G		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000392460.1

Frequencies

GnomAD3 genomes

AF:

0.866

AC:

131644

AN:

151984

Hom.:

57279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.954

Gnomad AMI

AF:

0.785

Gnomad AMR

AF:

0.848

Gnomad ASJ

AF:

0.904

Gnomad EAS

AF:

0.890

Gnomad SAS

AF:

0.879

Gnomad FIN

AF:

0.813

Gnomad MID

AF:

0.896

Gnomad NFE

AF:

0.821

Gnomad OTH

AF:

0.883

GnomAD2 exomes

AF:

0.847

AC:

210894

AN:

249042

AF XY:

0.848

show subpopulations

Gnomad AFR exome

AF:

0.957

Gnomad AMR exome

AF:

0.814

Gnomad ASJ exome

AF:

0.909

Gnomad EAS exome

AF:

0.883

Gnomad FIN exome

AF:

0.819

Gnomad NFE exome

AF:

0.828

Gnomad OTH exome

AF:

0.860

GnomAD4 exome

AF:

0.831

AC:

1214542

AN:

1461208

Hom.:

505815

Cov.:

AF XY:

0.832

AC XY:

604843

AN XY:

726898

show subpopulations

African (AFR)

AF:

0.959

AC:

32117

AN:

33480

American (AMR)

AF:

0.820

AC:

36667

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.907

AC:

23711

AN:

26136

East Asian (EAS)

AF:

0.893

AC:

35455

AN:

39700

South Asian (SAS)

AF:

0.870

AC:

75063

AN:

86256

European-Finnish (FIN)

AF:

0.820

AC:

43438

AN:

52992

Middle Eastern (MID)

AF:

0.908

AC:

5237

AN:

5768

European-Non Finnish (NFE)

AF:

0.819

AC:

910984

AN:

1111786

Other (OTH)

AF:

0.859

AC:

51870

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

12155

24309

36464

48618

60773

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20976

41952

62928

83904

104880

<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:

131767

AN:

152102

Hom.:

57341

Cov.:

AF XY:

0.866

AC XY:

64417

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.954

AC:

39617

AN:

41512

American (AMR)

AF:

0.848

AC:

12956

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.904

AC:

3138

AN:

3470

East Asian (EAS)

AF:

0.890

AC:

4581

AN:

5150

South Asian (SAS)

AF:

0.879

AC:

4233

AN:

4818

European-Finnish (FIN)

AF:

0.813

AC:

8605

AN:

10580

Middle Eastern (MID)

AF:

0.901

AC:

265

AN:

294

European-Non Finnish (NFE)

AF:

0.821

AC:

55794

AN:

67982

Other (OTH)

AF:

0.884

AC:

1864

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

881

1761

2642

3522

4403

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:

0.830

Hom.:

13106

Bravo

AF:

0.874

TwinsUK

AF:

0.815

AC:

3023

ALSPAC

AF:

0.821

AC:

3164

ESP6500AA

AF:

0.955

AC:

3789

ESP6500EA

AF:

0.826

AC:

6842

ExAC

AF:

0.848

AC:

102396

Asia WGS

AF:

0.906

AC:

3151

AN:

3478

EpiCase

AF:

0.843

EpiControl

AF:

0.847

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

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.0093

T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.057

T;T

MetaRNN

Benign

7.7e-7

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.3

N;.

PhyloP100

2.2

PrimateAI

Benign

0.35

PROVEAN

Benign

1.0

N;.

REVEL

Benign

0.082

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.023

MPC

0.14

ClinPred

0.0052

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.027

gMVP

0.091

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over