X-56994641-T-C

Variant names:

• chrX-56994641-T-C
• rs749681460
• NM_001010862.3:c.307A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001010862.3(SPIN3):​c.307A>G​(p.Arg103Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: SPIN3 NM_001010862.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.08

Genes affected

SPIN3 (HGNC:27272): (spindlin family member 3) Enables methylated histone binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be integral component of membrane. Predicted to be active in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPIN3	NM_001010862.3	c.307A>G	p.Arg103Gly	missense_variant	Exon 2 of 2	ENST00000374919.6	NP_001010862.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPIN3	ENST00000374919.6	c.307A>G	p.Arg103Gly	missense_variant	Exon 2 of 2	1	NM_001010862.3	ENSP00000364054.3
SPIN3	ENST00000639257.1	n.225+82A>G		intron_variant	Intron 2 of 4	3		ENSP00000492259.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.307A>G (p.R103G) alteration is located in exon 2 (coding exon 1) of the SPIN3 gene. This alteration results from a A to G substitution at nucleotide position 307, causing the arginine (R) at amino acid position 103 to be replaced by a glycine (G). 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	Pathogenic	0.91
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T;T;T;T;T;T
FATHMM_MKL	Benign	0.69	D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.45	T;T;T;T;T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.2	M;M;M;M;M;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-6.0	D;.;.;.;.;.
REVEL	Benign	0.21
Sift	Uncertain	0.0080	D;.;.;.;.;.
Sift4G	Uncertain	0.027	D;.;.;.;.;.
Polyphen		1.0	D;D;D;D;D;D
Vest4		0.61
MutPred		0.39		Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);
MVP		0.35
MPC		1.1
ClinPred		0.98	D
GERP RS		2.5
Varity_R		0.80
gMVP		0.89

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: rs749681460; hg19: chrX-57021074;