17-745069-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_015721.3(GEMIN4):ā€‹c.2974A>Gā€‹(p.Met992Val) variant causes a missense change. The variant allele was found at a frequency of 0.000559 in 1,613,690 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0031 ( 2 hom., cov: 33)
Exomes š‘“: 0.00029 ( 2 hom. )

Consequence

GEMIN4
NM_015721.3 missense

Scores

2
8
8

Clinical Significance

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

Conservation

PhyloP100: 7.16
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.011332035).
BP6
Variant 17-745069-T-C is Benign according to our data. Variant chr17-745069-T-C is described in ClinVar as [Benign]. Clinvar id is 734199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GEMIN4NM_015721.3 linkuse as main transcriptc.2974A>G p.Met992Val missense_variant 2/2 ENST00000319004.6 NP_056536.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GEMIN4ENST00000319004.6 linkuse as main transcriptc.2974A>G p.Met992Val missense_variant 2/21 NM_015721.3 ENSP00000321706 P1
GEMIN4ENST00000576778.1 linkuse as main transcriptc.2941A>G p.Met981Val missense_variant 1/1 ENSP00000459565

Frequencies

GnomAD3 genomes
AF:
0.00310
AC:
472
AN:
152160
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0108
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000785
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00383
GnomAD3 exomes
AF:
0.000834
AC:
207
AN:
248348
Hom.:
2
AF XY:
0.000593
AC XY:
80
AN XY:
134866
show subpopulations
Gnomad AFR exome
AF:
0.0111
Gnomad AMR exome
AF:
0.000784
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000982
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000267
Gnomad OTH exome
AF:
0.000663
GnomAD4 exome
AF:
0.000294
AC:
430
AN:
1461412
Hom.:
2
Cov.:
61
AF XY:
0.000239
AC XY:
174
AN XY:
726974
show subpopulations
Gnomad4 AFR exome
AF:
0.0103
Gnomad4 AMR exome
AF:
0.000739
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000989
Gnomad4 OTH exome
AF:
0.000613
GnomAD4 genome
AF:
0.00310
AC:
472
AN:
152278
Hom.:
2
Cov.:
33
AF XY:
0.00283
AC XY:
211
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.0107
Gnomad4 AMR
AF:
0.000784
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00379
Alfa
AF:
0.000742
Hom.:
1
Bravo
AF:
0.00336
ESP6500AA
AF:
0.00857
AC:
35
ESP6500EA
AF:
0.000119
AC:
1
ExAC
AF:
0.000802
AC:
97
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenApr 01, 2024GEMIN4: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Uncertain
-0.060
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.23
T;.
Eigen
Uncertain
0.67
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.77
T;T
MetaRNN
Benign
0.011
T;T
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.3
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.47
T
PROVEAN
Uncertain
-3.1
D;.
REVEL
Uncertain
0.33
Sift
Pathogenic
0.0
D;.
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.99
D;.
Vest4
0.77
MVP
0.67
MPC
0.60
ClinPred
0.031
T
GERP RS
5.8
Varity_R
0.72
gMVP
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs114237735; hg19: chr17-648309; API