NM_001042479.2:c.623G>A

Variant names:

• chrX-14009019-C-T
• rs755568932
• NM_001042479.2:c.623G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001042479.2(GEMIN8):​c.623G>A​(p.Ser208Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,097,931 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.000017 (0 hom. 17 hem.)
• Consequence: GEMIN8 NM_001042479.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.81
• Publications: 0 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1937131).
• BS2: High Hemizygotes in GnomAdExome4 at 17 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.623G>A	p.Ser208Asn	missense	Exon 5 of 5	NP_001035944.1	Q9NWZ8
	GEMIN8	NM_001042480.2		c.623G>A	p.Ser208Asn	missense	Exon 4 of 4	NP_001035945.1	Q9NWZ8
	GEMIN8	NM_017856.3		c.623G>A	p.Ser208Asn	missense	Exon 5 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.623G>A	p.Ser208Asn	missense	Exon 5 of 5	ENSP00000505429.1	Q9NWZ8
	GEMIN8	ENST00000398355.7	TSL:1	c.623G>A	p.Ser208Asn	missense	Exon 4 of 4	ENSP00000381398.3	Q9NWZ8
	GEMIN8	ENST00000380523.8	TSL:2	c.623G>A	p.Ser208Asn	missense	Exon 5 of 5	ENSP00000369895.4	Q9NWZ8

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.0000273 AC: 5 AN: 183480 AF XY: 0.0000589

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: 0.0000173 AC: 19 AN: 1097931 Hom.: 0 Cov.: 30 AF XY: 0.0000468 AC XY: 17 AN XY: 363287

African (AFR) AF: 0.00 AC: 0 AN: 26396

American (AMR) AF: 0.00 AC: 0 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

East Asian (EAS) AF: 0.00 AC: 0 AN: 30204

South Asian (SAS) AF: 0.000332 AC: 18 AN: 54140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4125

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841859

Other (OTH) AF: 0.0000217 AC: 1 AN: 46084

GnomAD4 genome Cov.: 24

ExAC AF: 0.0000165 AC: 2

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	0.21
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.8
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.16
Sift	Benign	0.21	T
Sift4G	Benign	0.32	T
Polyphen		0.87	P
Vest4		0.079
MutPred		0.29		Gain of relative solvent accessibility (P = 0.0215)
MVP		0.69
MPC		1.1
ClinPred		0.29	T
GERP RS		5.4
Varity_R		0.18
gMVP		0.85
Mutation Taster		=96/4	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: rs755568932; hg19: chrX-14027138;