X-14009087-C-T

Variant names:

• chrX-14009087-C-T
• rs368722951
• NM_001042479.2:c.555G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001042479.2(GEMIN8):​c.555G>A​(p.Ser185Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000545 in 1,210,659 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., 6 hem., cov: 23)
  • Exomes 𝑓: 0.000045 (0 hom. 15 hem.)
• Consequence: GEMIN8 NM_001042479.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.28
• Publications: 1 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant X-14009087-C-T is Benign according to our data. Variant chrX-14009087-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2660035.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.28 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 6 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.555G>A	p.Ser185Ser	synonymous	Exon 5 of 5	NP_001035944.1	Q9NWZ8
	GEMIN8	NM_001042480.2		c.555G>A	p.Ser185Ser	synonymous	Exon 4 of 4	NP_001035945.1	Q9NWZ8
	GEMIN8	NM_017856.3		c.555G>A	p.Ser185Ser	synonymous	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.555G>A	p.Ser185Ser	synonymous	Exon 5 of 5	ENSP00000505429.1	Q9NWZ8
	GEMIN8	ENST00000398355.7	TSL:1	c.555G>A	p.Ser185Ser	synonymous	Exon 4 of 4	ENSP00000381398.3	Q9NWZ8
	GEMIN8	ENST00000380523.8	TSL:2	c.555G>A	p.Ser185Ser	synonymous	Exon 5 of 5	ENSP00000369895.4	Q9NWZ8

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 17 AN: 112741 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000322

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00392

Gnomad SAS AF: 0.000363

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000136 AC: 25 AN: 183369 AF XY: 0.0000884

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00159

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000446 AC: 49 AN: 1097866 Hom.: 0 Cov.: 30 AF XY: 0.0000413 AC XY: 15 AN XY: 363226

African (AFR) AF: 0.00 AC: 0 AN: 26395

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19384

East Asian (EAS) AF: 0.000861 AC: 26 AN: 30204

South Asian (SAS) AF: 0.000148 AC: 8 AN: 54139

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40529

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4137

European-Non Finnish (NFE) AF: 0.00000475 AC: 4 AN: 841788

Other (OTH) AF: 0.000217 AC: 10 AN: 46083

GnomAD4 genome AF: 0.000151 AC: 17 AN: 112793 Hom.: 0 Cov.: 23 AF XY: 0.000172 AC XY: 6 AN XY: 34939

African (AFR) AF: 0.0000321 AC: 1 AN: 31114

American (AMR) AF: 0.00 AC: 0 AN: 10709

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2658

East Asian (EAS) AF: 0.00393 AC: 14 AN: 3563

South Asian (SAS) AF: 0.000365 AC: 1 AN: 2743

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6242

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53313

Other (OTH) AF: 0.00 AC: 0 AN: 1543

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.0000416

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.046
DANN	Benign	0.67
PhyloP100		-5.3
Mutation Taster		=100/0	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: rs368722951; hg19: chrX-14027206;