chrX-14020459-C-G

Variant names:

• chrX-14020459-C-G
• rs61740319
• NM_001042479.2:c.91G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001042479.2(GEMIN8):​c.91G>C​(p.Ala31Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000498 in 1,205,692 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. 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. A31S) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000046 (0 hom. 2 hem.)
• Consequence: GEMIN8 NM_001042479.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.98
• Publications: 5 publications found

Genes affected

GEMIN8 (HGNC:26044): (gem nuclear organelle associated protein 8) The protein encoded by this gene is part of the SMN complex, which is necessary for spliceosomal snRNP assembly in the cytoplasm and pre-mRNA splicing in the nucleus. The encoded protein binds to both SMN1 and the GEMIN6/GEMIN7 heterodimer, mediating their interaction. This protein is found in nuclear Gemini of Cajal bodies (gems) and in the cytoplasm. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, May 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042479.2. 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
	GEMIN8	NM_001042479.2	MANE Select	c.91G>C	p.Ala31Pro	missense	Exon 4 of 5	NP_001035944.1	Q9NWZ8
	GEMIN8	NM_001042480.2		c.91G>C	p.Ala31Pro	missense	Exon 3 of 4	NP_001035945.1	Q9NWZ8
	GEMIN8	NM_017856.3		c.91G>C	p.Ala31Pro	missense	Exon 4 of 5	NP_060326.1	Q9NWZ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GEMIN8	ENST00000680255.1	MANE Select	c.91G>C	p.Ala31Pro	missense	Exon 4 of 5	ENSP00000505429.1	Q9NWZ8
	GEMIN8	ENST00000398355.7	TSL:1	c.91G>C	p.Ala31Pro	missense	Exon 3 of 4	ENSP00000381398.3	Q9NWZ8
	GEMIN8	ENST00000380523.8	TSL:2	c.91G>C	p.Ala31Pro	missense	Exon 4 of 5	ENSP00000369895.4	Q9NWZ8

Frequencies

GnomAD3 genomes AF: 0.00000893 AC: 1 AN: 112025 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000457 AC: 5 AN: 1093667 Hom.: 0 Cov.: 28 AF XY: 0.00000557 AC XY: 2 AN XY: 359173

African (AFR) AF: 0.00 AC: 0 AN: 26315

American (AMR) AF: 0.00 AC: 0 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19355

East Asian (EAS) AF: 0.00 AC: 0 AN: 30196

South Asian (SAS) AF: 0.00 AC: 0 AN: 54039

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4124

European-Non Finnish (NFE) AF: 0.00000597 AC: 5 AN: 837978

Other (OTH) AF: 0.00 AC: 0 AN: 45929

GnomAD4 genome AF: 0.00000893 AC: 1 AN: 112025 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34185

African (AFR) AF: 0.00 AC: 0 AN: 30799

American (AMR) AF: 0.00 AC: 0 AN: 10595

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3588

South Asian (SAS) AF: 0.00 AC: 0 AN: 2677

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6115

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53174

Other (OTH) AF: 0.00 AC: 0 AN: 1506

Alfa AF: 0.00 Hom.: 39

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Pathogenic	0.33	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.040	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.47		Loss of MoRF binding (P = 0.0602)
MVP		0.54
MPC		1.3
ClinPred		0.99	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.92
gMVP		0.85
Mutation Taster		=58/42	polymorphism

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: rs61740319; hg19: chrX-14038578;