X-63350108-T-C

Variant names:

• chrX-63350108-T-C
• rs1382396052
• NM_001012968.3:c.712A>G

Variant summary

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

The NM_001012968.3(SPIN4):​c.712A>G​(p.Ile238Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000892 in 112,126 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
• Consequence: SPIN4 NM_001012968.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.34
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12096283).

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.712A>G	p.Ile238Val	missense	Exon 1 of 1	NP_001012986.2	Q56A73
	SPIN4-AS1	NR_046739.1		n.298+374T>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.712A>G	p.Ile238Val	missense	Exon 1 of 1	ENSP00000364018.3	Q56A73
	SPIN4-AS1	ENST00000451979.1	TSL:2	n.89+374T>C		intron	N/A
	LINC01278	ENST00000610088.6	TSL:4	n.492-6819A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000892 AC: 1 AN: 112126 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000892 AC: 1 AN: 112126 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34274

African (AFR) AF: 0.00 AC: 0 AN: 30821

American (AMR) AF: 0.00 AC: 0 AN: 10633

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3559

South Asian (SAS) AF: 0.00 AC: 0 AN: 2677

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6055

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53302

Other (OTH) AF: 0.00 AC: 0 AN: 1504

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.11
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	19
DANN	Benign	0.67
DEOGEN2	Benign	0.0075	T
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.42	N
PhyloP100		5.3
PrimateAI	Uncertain	0.52	T
REVEL	Benign	0.13
Polyphen		0.0010	B
MutPred		0.27		Gain of ubiquitination at K233 (P = 0.1204)
MVP		0.13
ClinPred		0.095	T
GERP RS		3.8
Varity_R		0.10
gMVP		0.79
Mutation Taster		=79/21	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: rs1382396052; hg19: chrX-62569987;