X-63350270-A-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/18 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08452976).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPIN4	NM_001012968.3	c.550T>C	p.Tyr184His	missense_variant	Exon 1 of 1	ENST00000374884.3	NP_001012986.2
SPIN4-AS1	NR_046739.1	n.298+536A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPIN4	ENST00000374884.3	c.550T>C	p.Tyr184His	missense_variant	Exon 1 of 1	6	NM_001012968.3	ENSP00000364018.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.550T>C (p.Y184H) alteration is located in exon 1 (coding exon 1) of the SPIN4 gene. This alteration results from a T to C substitution at nucleotide position 550, causing the tyrosine (Y) at amino acid position 184 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-62570149;