X-14003688-C-T

Variant names:

• chrX-14003688-C-T
• rs1557726
• ENST00000965135.1:c.*43-4738G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000965135.1(GEMIN8):​c.*43-4738G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 111,157 control chromosomes in the GnomAD database, including 3,356 homozygotes. There are 9,194 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 0.28 (3356 hom., 9194 hem., cov: 23)
• Consequence: GEMIN8 ENST00000965135.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000965135.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GEMIN8	ENST00000965135.1		c.*43-4738G>A		intron	N/A	ENSP00000635194.1
	GEMIN8	ENST00000850642.1		n.*138-284G>A		intron	N/A	ENSP00000520921.1	A0ABB0MVM6

Frequencies

GnomAD3 genomes AF: 0.284 AC: 31568 AN: 111102 Hom.: 3356 Cov.: 23

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.0114

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.256

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.284 AC: 31566 AN: 111157 Hom.: 3356 Cov.: 23 AF XY: 0.275 AC XY: 9194 AN XY: 33411

African (AFR) AF: 0.305 AC: 9332 AN: 30585

American (AMR) AF: 0.222 AC: 2330 AN: 10482

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 648 AN: 2634

East Asian (EAS) AF: 0.0111 AC: 40 AN: 3601

South Asian (SAS) AF: 0.294 AC: 779 AN: 2651

European-Finnish (FIN) AF: 0.280 AC: 1645 AN: 5878

Middle Eastern (MID) AF: 0.242 AC: 52 AN: 215

European-Non Finnish (NFE) AF: 0.305 AC: 16156 AN: 52923

Other (OTH) AF: 0.253 AC: 384 AN: 1520

Alfa AF: 0.283 Hom.: 1975

Bravo AF: 0.280

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.45
DANN	Benign	0.28
PhyloP100		-0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1557726; hg19: chrX-14021807;