rs7057480

Positions:

• chrX-14026123-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042479.2(GEMIN8):​c.-34+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 744,695 control chromosomes in the GnomAD database, including 23,136 homozygotes. There are 64,827 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (2747 hom., 8260 hem., cov: 23)
  • Exomes 𝑓: 0.30 (20389 hom. 56567 hem.)
• Consequence: GEMIN8 NM_001042479.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GEMIN8	NM_001042479.2	c.-34+17C>T		intron_variant		ENST00000680255.1	NP_001035944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GEMIN8	ENST00000680255.1	c.-34+17C>T		intron_variant			NM_001042479.2	ENSP00000505429	P1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 28398 AN: 111123 Hom.: 2747 Cov.: 23 AF XY: 0.248 AC XY: 8258 AN XY: 33351

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.0115

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.301 AC: 190816 AN: 633519 Hom.: 20389 Cov.: 13 AF XY: 0.305 AC XY: 56567 AN XY: 185643

Gnomad4 AFR exome AF: 0.206

Gnomad4 AMR exome AF: 0.185

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.0103

Gnomad4 SAS exome AF: 0.332

Gnomad4 FIN exome AF: 0.240

Gnomad4 NFE exome AF: 0.305

Gnomad4 OTH exome AF: 0.280

GnomAD4 genome AF: 0.255 AC: 28395 AN: 111176 Hom.: 2747 Cov.: 23 AF XY: 0.247 AC XY: 8260 AN XY: 33414

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.0112

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.234

Alfa AF: 0.273 Hom.: 4652

Bravo AF: 0.247

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.1
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs7057480; hg19: chrX-14044242;