chr5-154917235-A-C

Variant names:

• chr5-154917235-A-C
• rs348735
• NM_015465.5:c.1674-56T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.784
• Publications: 5 publications found

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015465.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GEMIN5	NM_015465.5	MANE Select	c.1674-56T>G		intron	N/A	NP_056280.2
	GEMIN5	NM_001252156.2		c.1671-56T>G		intron	N/A	NP_001239085.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GEMIN5	ENST00000285873.8	TSL:1 MANE Select	c.1674-56T>G		intron	N/A	ENSP00000285873.6

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

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: 94 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

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

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: 44 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

Alfa AF: 0.515 Hom.: 12189

Bravo AF: 0.437

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.23
PhyloP100		0.78
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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