rs348735

Positions:

• chr5-154917235-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000285873.8(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 ENST00000285873.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.784

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GEMIN5	NM_015465.5	c.1674-56T>G		intron_variant		ENST00000285873.8	NP_056280.2
GEMIN5	NM_001252156.2	c.1671-56T>G		intron_variant			NP_001239085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GEMIN5	ENST00000285873.8	c.1674-56T>G		intron_variant		1	NM_015465.5	ENSP00000285873	P1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69438 AN: 151912 Hom.: 17010 Cov.: 32

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

Gnomad4 AFR exome AF: 0.375

Gnomad4 AMR exome AF: 0.254

Gnomad4 ASJ exome AF: 0.545

Gnomad4 EAS exome AF: 0.00302

Gnomad4 SAS exome AF: 0.312

Gnomad4 FIN exome AF: 0.524

Gnomad4 NFE exome AF: 0.550

Gnomad4 OTH exome AF: 0.476

GnomAD4 genome AF: 0.457 AC: 69453 AN: 152030 Hom.: 17010 Cov.: 32 AF XY: 0.452 AC XY: 33560 AN XY: 74306

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.00848

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.456

Alfa AF: 0.514 Hom.: 10992

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
DANN	Benign	0.23

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

Other links and lift over

dbSNP: rs348735; hg19: chr5-154296795; COSMIC: COSV53560403;