X-14026123-G-C

Variant names:

• chrX-14026123-G-C
• rs7057480
• NM_001042479.2:c.-34+17C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001042479.2(GEMIN8):​c.-34+17C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000316 in 633,907 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: not found (cov: 23)
  • Exomes 𝑓: 0.0000032 (0 hom. 0 hem.)
• Consequence: GEMIN8 NM_001042479.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GEMIN8	NM_001042479.2	c.-34+17C>G		intron_variant	Intron 2 of 4	ENST00000680255.1	NP_001035944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GEMIN8	ENST00000680255.1	c.-34+17C>G		intron_variant	Intron 2 of 4		NM_001042479.2	ENSP00000505429.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000316 AC: 2 AN: 633907 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 185651

African (AFR) AF: 0.00 AC: 0 AN: 12266

American (AMR) AF: 0.00 AC: 0 AN: 810

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3927

East Asian (EAS) AF: 0.00 AC: 0 AN: 2998

South Asian (SAS) AF: 0.00 AC: 0 AN: 11832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1087

European-Non Finnish (NFE) AF: 0.00000345 AC: 2 AN: 579448

Other (OTH) AF: 0.00 AC: 0 AN: 20949

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.50
PhyloP100		0.075

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: rs7057480; hg19: chrX-14044242;