rs1924217058

Variant names:

• chrX-14020281-G-A
• rs1924217058
• NM_001042479.2:c.269C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-14020281-G-A
• chrX-14020281-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001042479.2(GEMIN8):​c.269C>T​(p.Ser90Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000365 in 1,096,854 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S90C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000036 (0 hom. 1 hem.)
• Consequence: GEMIN8 NM_001042479.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06877014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GEMIN8	NM_001042479.2	c.269C>T	p.Ser90Phe	missense_variant	Exon 4 of 5	ENST00000680255.1	NP_001035944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GEMIN8	ENST00000680255.1	c.269C>T	p.Ser90Phe	missense_variant	Exon 4 of 5		NM_001042479.2	ENSP00000505429.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000365 AC: 4 AN: 1096854 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 1 AN XY: 362214

African (AFR) AF: 0.000114 AC: 3 AN: 26375

American (AMR) AF: 0.00 AC: 0 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19377

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

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54118

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 840859

Other (OTH) AF: 0.00 AC: 0 AN: 46053

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.19
DANN	Benign	0.20
DEOGEN2	Benign	0.013	T;T;T
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.54	.;T;T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.069	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;.
PhyloP100		-0.51
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.053
Sift	Benign	0.68	T;T;T
Sift4G	Benign	0.68	T;T;T
Polyphen		0.42	B;B;.
Vest4		0.16
MutPred		0.24		Loss of disorder (P = 0.0116);Loss of disorder (P = 0.0116);Loss of disorder (P = 0.0116);
MVP		0.21
MPC		0.45
ClinPred		0.12	T
GERP RS		-1.5
Varity_R		0.068
gMVP		0.11
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1924217058; hg19: chrX-14038400;