Variant chr17-744946-G-A 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.3097C>T(p.Arg1033Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.588 in 1,613,538 control chromosomes in the GnomAD database, including 283,455 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.66 ( 34059 hom., cov: 34)

Exomes 𝑓: 0.58 ( 249396 hom. )

Consequence

GEMIN4
NM_015721.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.33

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.9635254E-6).

BP6

Variant 17-744946-G-A is Benign according to our data. Variant chr17-744946-G-A is described in ClinVar as [Benign]. Clinvar id is 1182789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GEMIN4	NM_015721.3 linkuse as main transcript	c.3097C>T	p.Arg1033Cys	missense_variant	2/2	ENST00000319004.6	NP_056536.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GEMIN4	ENST00000319004.6 linkuse as main transcript	c.3097C>T	p.Arg1033Cys	missense_variant	2/2	1	NM_015721.3	ENSP00000321706	P1
GEMIN4	ENST00000576778.1 linkuse as main transcript	c.3064C>T	p.Arg1022Cys	missense_variant	1/1			ENSP00000459565

Frequencies

GnomAD3 genomes

AF:

0.658

AC:

100061

AN:

152088

Hom.:

34005

Cov.:

show subpopulations

Gnomad AFR

AF:

0.831

Gnomad AMI

AF:

0.377

Gnomad AMR

AF:

0.679

Gnomad ASJ

AF:

0.630

Gnomad EAS

AF:

0.705

Gnomad SAS

AF:

0.639

Gnomad FIN

AF:

0.623

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.556

Gnomad OTH

AF:

0.660

GnomAD3 exomes

AF:

0.627

AC:

155780

AN:

248288

Hom.:

49784

AF XY:

0.624

AC XY:

84063

AN XY:

134822

show subpopulations

Gnomad AFR exome

AF:

0.833

Gnomad AMR exome

AF:

0.691

Gnomad ASJ exome

AF:

0.632

Gnomad EAS exome

AF:

0.701

Gnomad SAS exome

AF:

0.657

Gnomad FIN exome

AF:

0.625

Gnomad NFE exome

AF:

0.560

Gnomad OTH exome

AF:

0.633

GnomAD4 exome

AF:

0.580

AC:

848250

AN:

1461332

Hom.:

249396

Cov.:

AF XY:

0.582

AC XY:

422987

AN XY:

726946

show subpopulations

Gnomad4 AFR exome

AF:

0.841

Gnomad4 AMR exome

AF:

0.689

Gnomad4 ASJ exome

AF:

0.634

Gnomad4 EAS exome

AF:

0.676

Gnomad4 SAS exome

AF:

0.659

Gnomad4 FIN exome

AF:

0.627

Gnomad4 NFE exome

AF:

0.553

Gnomad4 OTH exome

AF:

0.614

GnomAD4 genome

AF:

0.658

AC:

100173

AN:

152206

Hom.:

34059

Cov.:

AF XY:

0.660

AC XY:

49111

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.831

Gnomad4 AMR

AF:

0.679

Gnomad4 ASJ

AF:

0.630

Gnomad4 EAS

AF:

0.704

Gnomad4 SAS

AF:

0.639

Gnomad4 FIN

AF:

0.623

Gnomad4 NFE

AF:

0.555

Gnomad4 OTH

AF:

0.663

Alfa

AF:

0.583

Hom.:

37384

Bravo

AF:

0.672

TwinsUK

AF:

0.541

AC:

2007

ALSPAC

AF:

0.552

AC:

2129

ESP6500AA

AF:

0.836

AC:

3317

ESP6500EA

AF:

0.563

AC:

4676

ExAC

AF:

0.623

AC:

75292

Asia WGS

AF:

0.691

AC:

2401

AN:

3478

EpiCase

AF:

0.583

EpiControl

AF:

0.587

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 03, 2020	This variant is associated with the following publications: (PMID: 19047128, 21766210, 20732906, 21118967) -

Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.77

T;T

MetaRNN

Benign

0.0000020

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

0.90

L;.

MutationTaster

Benign

0.000018

P;P

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.2

D;.

REVEL

Benign

0.19

Sift

Uncertain

0.0050

D;.

Sift4G

Uncertain

0.011

D;D

Polyphen

0.99

D;.

Vest4

0.28

MPC

0.56

ClinPred

0.034

GERP RS

5.7

Varity_R

0.29

gMVP

0.22

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