NM_001012968.3:c.550T>C

Variant names:

• chrX-63350270-A-G
• rs781948942
• NM_001012968.3:c.550T>C

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.550T>C​(p.Tyr184His) 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. 13/19 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: 1.09
• 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=0.08452976).

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.550T>C	p.Tyr184His	missense	Exon 1 of 1	NP_001012986.2	Q56A73
	SPIN4-AS1	NR_046739.1		n.298+536A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPIN4	ENST00000374884.3	TSL:6 MANE Select	c.550T>C	p.Tyr184His	missense	Exon 1 of 1	ENSP00000364018.3	Q56A73
	SPIN4-AS1	ENST00000451979.1	TSL:2	n.89+536A>G		intron	N/A
	LINC01278	ENST00000610088.6	TSL:4	n.492-6981T>C		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	0.12
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.1
PrimateAI	Uncertain	0.59	T
REVEL	Benign	0.075
Polyphen		0.0	B
MutPred		0.44		Loss of phosphorylation at Y184 (P = 0.0173)
MVP		0.14
ClinPred		0.21	T
GERP RS		3.8
Varity_R		0.19
gMVP		0.22
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: rs781948942; hg19: chrX-62570149;