X-63350551-T-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 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

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 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPIN4	NM_001012968.3	c.269A>G	p.His90Arg	missense_variant	Exon 1 of 1	ENST00000374884.3	NP_001012986.2
SPIN4-AS1	NR_046739.1	n.298+817T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPIN4	ENST00000374884.3	c.269A>G	p.His90Arg	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

May 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.269A>G (p.H90R) alteration is located in exon 1 (coding exon 1) of the SPIN4 gene. This alteration results from a A to G substitution at nucleotide position 269, causing the histidine (H) at amino acid position 90 to be replaced by an arginine (R). 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	0.26
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
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

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

LitVar

Other links and lift over

dbSNP: rs200724711; hg19: chrX-62570430;