NM_003616.3:c.710T>A

Variant names:

• chr14-39132067-T-A
• rs761395597
• NM_003616.3:c.710T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003616.3(GEMIN2):​c.710T>A​(p.Val237Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000315 in 1,271,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: GEMIN2 NM_003616.3 missense, splice_region
• Scores: Splicing: ADA: 0.02660
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.81
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23965073).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003616.3. 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
	GEMIN2	NM_003616.3	MANE Select	c.710T>A	p.Val237Glu	missense splice_region	Exon 8 of 10	NP_003607.2	O14893-5
	GEMIN2	NM_001009182.2		c.665T>A	p.Val222Glu	missense splice_region	Exon 7 of 9	NP_001009182.2	A0A8J9FJK1
	GEMIN2	NM_001009183.2		c.710T>A	p.Val237Glu	missense splice_region	Exon 8 of 9	NP_001009183.2	A0A8J9FN78

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GEMIN2	ENST00000308317.12	TSL:1 MANE Select	c.710T>A	p.Val237Glu	missense splice_region	Exon 8 of 10	ENSP00000308533.7	O14893-5
	GEMIN2	ENST00000250379.13	TSL:1	c.665T>A	p.Val222Glu	missense splice_region	Exon 7 of 9	ENSP00000250379.9	A0A8J9FJK1
	GEMIN2	ENST00000396249.7	TSL:1	c.710T>A	p.Val237Glu	missense splice_region	Exon 8 of 9	ENSP00000379548.3	A0A8J9FN78

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247760 AF XY: 0.00000748

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000315 AC: 4 AN: 1271634 Hom.: 0 Cov.: 19 AF XY: 0.00000467 AC XY: 3 AN XY: 641894

African (AFR) AF: 0.00 AC: 0 AN: 29800

American (AMR) AF: 0.00 AC: 0 AN: 44102

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24940

East Asian (EAS) AF: 0.00 AC: 0 AN: 38764

South Asian (SAS) AF: 0.0000366 AC: 3 AN: 81888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5446

European-Non Finnish (NFE) AF: 0.00000106 AC: 1 AN: 939346

Other (OTH) AF: 0.00 AC: 0 AN: 54052

GnomAD4 genome Cov.: 32

Alfa AF: 0.000111 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	0.0073	T
BayesDel_noAF	Benign	-0.12
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.084
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.8
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.12
Sift	Benign	0.10	T
Sift4G	Benign	0.18	T
Polyphen		0.015	B
Vest4		0.40
MutPred		0.50		Gain of solvent accessibility (P = 0.002)
MVP		0.76
MPC		0.25
ClinPred		0.37	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.62
gMVP		0.29
Mutation Taster		=43/57	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.027
dbscSNV1_RF	Benign	0.23
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: rs761395597; hg19: chr14-39601271;