X-14020293-T-G

Position:

• chrX-14020293-T-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001042479.2(GEMIN8):​c.257A>C​(p.Tyr86Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: GEMIN8 NM_001042479.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.103

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]

GEMIN8 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03338492).
• BP6: Variant X-14020293-T-G is Benign according to our data. Variant chrX-14020293-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3281216.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GEMIN8	NM_001042479.2	c.257A>C	p.Tyr86Ser	missense_variant	4/5	ENST00000680255.1	NP_001035944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GEMIN8	ENST00000680255.1	c.257A>C	p.Tyr86Ser	missense_variant	4/5		NM_001042479.2	ENSP00000505429.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 19, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.2
DANN	Benign	0.29
DEOGEN2	Benign	0.0016	T;T;T
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.23	.;T;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.033	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.3	N;N;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.28	N;N;N
REVEL	Benign	0.023
Sift	Benign	0.42	T;T;T
Sift4G	Benign	0.41	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.059
MutPred		0.23		Gain of disorder (P = 0.0062);Gain of disorder (P = 0.0062);Gain of disorder (P = 0.0062);
MVP		0.043
MPC		0.50
ClinPred		0.064	T
GERP RS		2.1
Varity_R		0.065
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-14038412;