rs200724711

Variant names:

• chrX-63350551-T-C
• rs200724711
• NM_001012968.3:c.269A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001012968.3(SPIN4):​c.269A>G​(p.His90Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: SPIN4 NM_001012968.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.81
• Publications: 0 publications found

Genes affected

SPIN4 (HGNC:27040): (spindlin family member 4) Enables methylated histone binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be active in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SPIN4-AS1 (HGNC:41177): (SPIN4 antisense RNA 1)

LINC01278 (HGNC:28090): (long intergenic non-protein coding RNA 1278)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30704606).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012968.3. 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
	SPIN4	NM_001012968.3	MANE Select	c.269A>G	p.His90Arg	missense	Exon 1 of 1	NP_001012986.2	Q56A73
	SPIN4-AS1	NR_046739.1		n.298+817T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPIN4	ENST00000374884.3	TSL:6 MANE Select	c.269A>G	p.His90Arg	missense	Exon 1 of 1	ENSP00000364018.3	Q56A73
	SPIN4-AS1	ENST00000451979.1	TSL:2	n.89+817T>C		intron	N/A
	LINC01278	ENST00000610088.6	TSL:4	n.492-7262A>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.8
PrimateAI	Uncertain	0.77	T
REVEL	Benign	0.15
Polyphen		0.74	P
MutPred		0.57		Loss of ubiquitination at K93 (P = 0.0401)
MVP		0.13
ClinPred		0.85	D
GERP RS		1.9
Varity_R		0.63
gMVP		0.91
Mutation Taster		=70/30	polymorphism

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: rs200724711; hg19: chrX-62570430;