rs768709775

Variant names:

• chr14-39114380-G-A
• rs768709775
• NM_003616.3:c.42G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-39114380-G-A
• chr14-39114380-G-C
• chr14-39114380-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003616.3(GEMIN2):​c.42G>A​(p.Met14Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GEMIN2 NM_003616.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.09

Genes affected

GEMIN2 (HGNC:10884): (gem nuclear organelle associated protein 2) This gene encodes one of the proteins found in the SMN complex, which consists of several gemin proteins and the protein known as the survival of motor neuron protein. The SMN complex is localized to a subnuclear compartment called gems (gemini of coiled bodies) and is required for assembly of spliceosomal snRNPs and for pre-mRNA splicing. This protein interacts directly with the survival of motor neuron protein and it is required for formation of the SMN complex. A knockout mouse targeting the mouse homolog of this gene exhibited disrupted snRNP assembly and motor neuron degeneration. [provided by RefSeq, Aug 2011]

LOC105370459 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GEMIN2	NM_003616.3	c.42G>A	p.Met14Ile	missense_variant	Exon 1 of 10	ENST00000308317.12	NP_003607.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GEMIN2	ENST00000308317.12	c.42G>A	p.Met14Ile	missense_variant	Exon 1 of 10	1	NM_003616.3	ENSP00000308533.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;.;.
Eigen	Uncertain	0.60
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.0061	T
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.2	M;M;M
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.015	D;D;D
Sift4G	Uncertain	0.030	D;D;D
Polyphen		0.88	P;D;D
Vest4		0.71
MutPred		0.55		Loss of disorder (P = 0.0196);Loss of disorder (P = 0.0196);Loss of disorder (P = 0.0196);
MVP		0.80
MPC		0.37
ClinPred		0.99	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.91
gMVP		0.33

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: rs768709775; hg19: chr14-39583584;