Variant 5-154891327-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_015465.5(GEMIN5):c.4176A>G(p.Gln1392Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,614,032 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 41 hom., cov: 30)

Exomes 𝑓: 0.0013 ( 42 hom. )

Consequence

GEMIN5
NM_015465.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.853

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 5-154891327-T-C is Benign according to our data. Variant chr5-154891327-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 776084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.853 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.012 (1821/152196) while in subpopulation AFR AF= 0.0423 (1758/41516). AF 95% confidence interval is 0.0407. There are 41 homozygotes in gnomad4. There are 848 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GEMIN5	NM_015465.5 link	c.4176A>G	p.Gln1392Gln	synonymous_variant	Exon 26 of 28	ENST00000285873.8	NP_056280.2
GEMIN5	NM_001252156.2 link	c.4173A>G	p.Gln1391Gln	synonymous_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.4176A>G	p.Gln1392Gln	synonymous_variant	Exon 26 of 28	1	NM_015465.5	ENSP00000285873.6		Q8TEQ6
GEMIN5	ENST00000522075.1 link	n.*107A>G		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1819

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0424

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00282

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00311

AC:

782

AN:

251454

Hom.:

AF XY:

0.00213

AC XY:

290

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0415

Gnomad AMR exome

AF:

0.00223

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000149

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00126

AC:

1838

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

790

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0435

Gnomad4 AMR exome

AF:

0.00228

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000899

Gnomad4 OTH exome

AF:

0.00278

GnomAD4 genome

AF:

0.0120

AC:

1821

AN:

152196

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

848

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0423

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00687

Hom.:

Bravo

AF:

0.0138

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000356

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 13, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction

Benign:1

May 17, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.2

DANN

Benign

0.15

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