5-154891257-T-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015465.5(GEMIN5):c.4246A>C(p.Ser1416Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000375 in 1,613,416 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00039 ( 9 hom. )

Consequence

GEMIN5
NM_015465.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.686

Variant links:

Genes affected

GEMIN5 (HGNC:20043): (gem nuclear organelle associated protein 5) This gene encodes a WD repeat protein that is a component of the survival of motor neurons (SMN) complex. The SMN complex plays a critical role in mRNA splicing through the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs), and may also mediate the assembly and transport of other classes of ribonucleoproteins. The encoded protein is the snRNA-binding component of the SMN complex. Dysregulation of this gene may play a role in alternative mRNA splicing and tumor cell motility. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

GEMIN5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004305899).

BP6

Variant 5-154891257-T-G is Benign according to our data. Variant chr5-154891257-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2655977.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000269 (41/152174) while in subpopulation SAS AF= 0.00728 (35/4808). AF 95% confidence interval is 0.00538. There are 0 homozygotes in gnomad4. There are 33 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GEMIN5	NM_015465.5 link	c.4246A>C	p.Ser1416Arg	missense_variant	Exon 26 of 28	ENST00000285873.8	NP_056280.2
GEMIN5	NM_001252156.2 link	c.4243A>C	p.Ser1415Arg	missense_variant	Exon 26 of 28		NP_001239085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GEMIN5	ENST00000285873.8 link	c.4246A>C	p.Ser1416Arg	missense_variant	Exon 26 of 28	1	NM_015465.5	ENSP00000285873.6		Q8TEQ6
GEMIN5	ENST00000522075.1 link	n.*177A>C		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00748

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000749

AC:

188

AN:

251100

Hom.:

AF XY:

0.00102

AC XY:

138

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00585

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000386

AC:

564

AN:

1461242

Hom.:

Cov.:

AF XY:

0.000550

AC XY:

400

AN XY:

726856

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00590

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000746

GnomAD4 genome

AF:

0.000269

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00728

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000572

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.000774

AC:

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

GEMIN5: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

CADD

Benign

6.2

DANN

Benign

0.94

DEOGEN2

Benign

0.0089

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.50

M_CAP

Benign

0.026

MetaRNN

Benign

0.0043

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.90

REVEL

Benign

0.15

Sift

Benign

0.25

Sift4G

Benign

0.25

Polyphen

0.22

Vest4

0.21

MutPred

0.12

Loss of loop (P = 0.0203);

MVP

0.40

MPC

0.082

ClinPred

0.0099

GERP RS

-7.3

Varity_R

0.045

gMVP

0.12

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.

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