Variant 17-746307-G-C 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.1736C>G(p.Ala579Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.588 in 1,613,454 control chromosomes in the GnomAD database, including 283,902 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 ( 34134 hom., cov: 32)

Exomes 𝑓: 0.58 ( 249768 hom. )

Consequence

GEMIN4
NM_015721.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 9.85

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=1.4544598E-6).

BP6

Variant 17-746307-G-C is Benign according to our data. Variant chr17-746307-G-C is described in ClinVar as [Benign]. Clinvar id is 1185309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 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.1736C>G	p.Ala579Gly	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.1736C>G	p.Ala579Gly	missense_variant	2/2	1	NM_015721.3	ENSP00000321706	P1
GEMIN4	ENST00000576778.1 linkuse as main transcript	c.1703C>G	p.Ala568Gly	missense_variant	1/1			ENSP00000459565

Frequencies

GnomAD3 genomes

AF:

0.659

AC:

100097

AN:

151908

Hom.:

34079

Cov.:

show subpopulations

Gnomad AFR

AF:

0.834

Gnomad AMI

AF:

0.377

Gnomad AMR

AF:

0.679

Gnomad ASJ

AF:

0.630

Gnomad EAS

AF:

0.706

Gnomad SAS

AF:

0.642

Gnomad FIN

AF:

0.623

Gnomad MID

AF:

0.766

Gnomad NFE

AF:

0.555

Gnomad OTH

AF:

0.660

GnomAD3 exomes

AF:

0.628

AC:

156240

AN:

248734

Hom.:

50054

AF XY:

0.624

AC XY:

84303

AN XY:

135026

show subpopulations

Gnomad AFR exome

AF:

0.837

Gnomad AMR exome

AF:

0.691

Gnomad ASJ exome

AF:

0.633

Gnomad EAS exome

AF:

0.702

Gnomad SAS exome

AF:

0.661

Gnomad FIN exome

AF:

0.625

Gnomad NFE exome

AF:

0.560

Gnomad OTH exome

AF:

0.634

GnomAD4 exome

AF:

0.581

AC:

848761

AN:

1461428

Hom.:

249768

Cov.:

AF XY:

0.582

AC XY:

423312

AN XY:

726976

show subpopulations

Gnomad4 AFR exome

AF:

0.845

Gnomad4 AMR exome

AF:

0.690

Gnomad4 ASJ exome

AF:

0.634

Gnomad4 EAS exome

AF:

0.676

Gnomad4 SAS exome

AF:

0.663

Gnomad4 FIN exome

AF:

0.627

Gnomad4 NFE exome

AF:

0.552

Gnomad4 OTH exome

AF:

0.615

GnomAD4 genome

AF:

0.659

AC:

100211

AN:

152026

Hom.:

34134

Cov.:

AF XY:

0.661

AC XY:

49104

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.835

Gnomad4 AMR

AF:

0.680

Gnomad4 ASJ

AF:

0.630

Gnomad4 EAS

AF:

0.706

Gnomad4 SAS

AF:

0.642

Gnomad4 FIN

AF:

0.623

Gnomad4 NFE

AF:

0.555

Gnomad4 OTH

AF:

0.663

Alfa

AF:

0.589

Hom.:

8710

Bravo

AF:

0.673

TwinsUK

AF:

0.540

AC:

2003

ALSPAC

AF:

0.553

AC:

2132

ESP6500AA

AF:

0.832

AC:

3341

ESP6500EA

AF:

0.563

AC:

4705

ExAC

AF:

0.624

AC:

75429

Asia WGS

AF:

0.692

AC:

2403

AN:

3478

EpiCase

AF:

0.583

EpiControl

AF:

0.585

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	clinical testing	GeneDx	Sep 16, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

0.12

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;.

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.91

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.66

T;T

MetaRNN

Benign

0.0000015

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

9.7e-9

P;P

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.4

D;.

REVEL

Uncertain

0.33

Sift

Uncertain

0.022

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.31

MPC

0.60

ClinPred

0.018

GERP RS

5.8

Varity_R

0.51

gMVP

0.38

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