dbSNP rs372573642: GEMIN4:p.Arg955Lys (chr17-745179-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_015721.3(GEMIN4):c.2864G>A(p.Arg955Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000361 in 1,606,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

GEMIN4
NM_015721.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.038753033).

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.2864G>A	p.Arg955Lys	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.2864G>A	p.Arg955Lys	missense	Exon 2 of 2	ENSP00000321706.5	P57678
	GEMIN4	ENST00000576778.1	TSL:6	c.2831G>A	p.Arg944Lys	missense	Exon 1 of 1	ENSP00000459565.1	I3L2C7

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000427

AC:

AN:

234322

AF XY:

0.0000392

show subpopulations

Gnomad AFR exome

AF:

0.000584

Gnomad AMR exome

AF:

0.0000608

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000220

AC:

AN:

1454140

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

722742

show subpopulations

African (AFR)

AF:

0.000540

AC:

AN:

33310

American (AMR)

AF:

0.0000689

AC:

AN:

43564

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25912

East Asian (EAS)

AF:

0.00

AC:

AN:

39382

South Asian (SAS)

AF:

0.00

AC:

AN:

85126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52068

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108860

Other (OTH)

AF:

0.000133

AC:

AN:

60156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000171

AC:

AN:

152292

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.000577

AC:

AN:

41564

American (AMR)

AF:

0.000131

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000197

Hom.:

Bravo

AF:

0.000181

ESP6500AA

AF:

0.000257

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000331

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.011

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.63

M_CAP

Benign

0.0032

MetaRNN

Benign

0.039

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.68

PhyloP100

1.4

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.31

REVEL

Benign

0.15

Sift

Benign

0.55

Sift4G

Benign

0.84

Polyphen

0.0010

Vest4

0.064

MVP

0.27

MPC

0.13

ClinPred

0.0081

GERP RS

4.5

Varity_R

0.059

gMVP

0.17

Mutation Taster

=92/8

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