5-154899279-G-C

Position:

• chr5-154899279-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015465.5(GEMIN5):​c.3046C>G​(p.Arg1016Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1016C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GEMIN5 NM_015465.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.14

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41540128).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GEMIN5	NM_015465.5	c.3046C>G	p.Arg1016Gly	missense_variant	22/28	ENST00000285873.8
GEMIN5	NM_001252156.2	c.3043C>G	p.Arg1015Gly	missense_variant	22/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GEMIN5	ENST00000285873.8	c.3046C>G	p.Arg1016Gly	missense_variant	22/28	1	NM_015465.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.00043	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	0.95	D
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.17
Sift	Benign	0.091	T
Sift4G	Benign	0.11	T
Polyphen		0.86	P
Vest4		0.56
MutPred		0.37		Loss of stability (P = 0.0316);
MVP		0.75
MPC		0.35
ClinPred		0.77	D
GERP RS		4.7
Varity_R		0.42
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61749643; hg19: chr5-154278839;