dbSNP rs348735: GEMIN5:c.1674-56T>G (chr5-154917235-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015465.5(GEMIN5):c.1674-56T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 1,016,848 control chromosomes in the GnomAD database, including 132,870 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 17010 hom., cov: 32)

Exomes 𝑓: 0.50 ( 115860 hom. )

Consequence

GEMIN5
NM_015465.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.784

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with cerebellar atrophy and motor dysfunction
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

GEMIN5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GEMIN5	NM_015465.5 link	c.1674-56T>G		intron_variant	Intron 12 of 27	ENST00000285873.8	NP_056280.2
GEMIN5	NM_001252156.2 link	c.1671-56T>G		intron_variant	Intron 12 of 27		NP_001239085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GEMIN5	ENST00000285873.8 link	c.1674-56T>G		intron_variant	Intron 12 of 27	1	NM_015465.5	ENSP00000285873.6		Q8TEQ6

Frequencies

GnomAD3 genomes

AF:

0.457

AC:

69438

AN:

151912

Hom.:

17010

Cov.:

show subpopulations

Gnomad AFR

AF:

0.382

Gnomad AMI

AF:

0.633

Gnomad AMR

AF:

0.374

Gnomad ASJ

AF:

0.538

Gnomad EAS

AF:

0.00846

Gnomad SAS

AF:

0.318

Gnomad FIN

AF:

0.519

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.549

Gnomad OTH

AF:

0.462

GnomAD4 exome

AF:

0.503

AC:

435321

AN:

864818

Hom.:

115860

AF XY:

0.501

AC XY:

216401

AN XY:

431534

show subpopulations

African (AFR)

AF:

0.375

AC:

7550

AN:

20120

American (AMR)

AF:

0.254

AC:

6355

AN:

25000

Ashkenazi Jewish (ASJ)

AF:

0.545

AC:

8609

AN:

15796

East Asian (EAS)

AF:

0.00302

AC:

AN:

31126

South Asian (SAS)

AF:

0.312

AC:

11169

AN:

35756

European-Finnish (FIN)

AF:

0.524

AC:

23025

AN:

43944

Middle Eastern (MID)

AF:

0.523

AC:

1877

AN:

3588

European-Non Finnish (NFE)

AF:

0.550

AC:

359061

AN:

652516

Other (OTH)

AF:

0.476

AC:

17581

AN:

36972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

10140

20280

30421

40561

50701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9730

19460

29190

38920

48650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.457

AC:

69453

AN:

152030

Hom.:

17010

Cov.:

AF XY:

0.452

AC XY:

33560

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.381

AC:

15811

AN:

41450

American (AMR)

AF:

0.373

AC:

5699

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.538

AC:

1865

AN:

3468

East Asian (EAS)

AF:

0.00848

AC:

AN:

5186

South Asian (SAS)

AF:

0.319

AC:

1540

AN:

4826

European-Finnish (FIN)

AF:

0.519

AC:

5480

AN:

10550

Middle Eastern (MID)

AF:

0.575

AC:

169

AN:

294

European-Non Finnish (NFE)

AF:

0.549

AC:

37304

AN:

67958

Other (OTH)

AF:

0.456

AC:

964

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1823

3645

5468

7290

9113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

622

1244

1866

2488

3110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.515

Hom.:

12189

Bravo

AF:

0.437

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.4

(source)

DANN

Benign

0.23

PhyloP100

0.78

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over