5-154931675-T-C

Variant names:

• chr5-154931675-T-C
• rs2644744
• NM_015465.5:c.662-98A>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.662-98A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 953,700 control chromosomes in the GnomAD database, including 378,536 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 0.83 (53654 hom., cov: 34)
  • Exomes 𝑓: 0.90 (324882 hom.)
• Consequence: GEMIN5 NM_015465.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 1 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: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.903 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GEMIN5	NM_015465.5	MANE Select	c.662-98A>G		intron	N/A	NP_056280.2	Q8TEQ6
	GEMIN5	NM_001252156.2		c.662-101A>G		intron	N/A	NP_001239085.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GEMIN5	ENST00000285873.8	TSL:1 MANE Select	c.662-98A>G		intron	N/A	ENSP00000285873.6	Q8TEQ6
	GEMIN5	ENST00000523355.1	TSL:4	n.42A>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126900 AN: 152138 Hom.: 53640 Cov.: 34

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.909

Gnomad OTH AF: 0.850

GnomAD4 exome AF: 0.899 AC: 720743 AN: 801444 Hom.: 324882 Cov.: 10 AF XY: 0.900 AC XY: 368114 AN XY: 409184

African (AFR) AF: 0.685 AC: 13074 AN: 19088

American (AMR) AF: 0.786 AC: 20494 AN: 26074

Ashkenazi Jewish (ASJ) AF: 0.911 AC: 15402 AN: 16902

East Asian (EAS) AF: 0.908 AC: 31729 AN: 34938

South Asian (SAS) AF: 0.882 AC: 49363 AN: 55962

European-Finnish (FIN) AF: 0.878 AC: 38486 AN: 43814

Middle Eastern (MID) AF: 0.869 AC: 3265 AN: 3756

European-Non Finnish (NFE) AF: 0.915 AC: 515599 AN: 563584

Other (OTH) AF: 0.893 AC: 33331 AN: 37326

GnomAD4 genome AF: 0.834 AC: 126955 AN: 152256 Hom.: 53654 Cov.: 34 AF XY: 0.833 AC XY: 62053 AN XY: 74452

African (AFR) AF: 0.684 AC: 28409 AN: 41508

American (AMR) AF: 0.814 AC: 12454 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 3165 AN: 3472

East Asian (EAS) AF: 0.912 AC: 4736 AN: 5192

South Asian (SAS) AF: 0.891 AC: 4305 AN: 4832

European-Finnish (FIN) AF: 0.863 AC: 9150 AN: 10600

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.909 AC: 61871 AN: 68038

Other (OTH) AF: 0.850 AC: 1798 AN: 2116

Alfa AF: 0.860 Hom.: 8261

Bravo AF: 0.822

Asia WGS AF: 0.876 AC: 3044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	14
DANN	Benign	0.69
PhyloP100		1.2
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: rs2644744; hg19: chr5-154311235;