chrX-56994377-C-T

Variant names:

• chrX-56994377-C-T
• rs772664485
• NM_001010862.3:c.571G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001010862.3(SPIN3):​c.571G>A​(p.Asp191Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,098,012 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: SPIN3 NM_001010862.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.13

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29277346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPIN3	NM_001010862.3	c.571G>A	p.Asp191Asn	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.571G>A	p.Asp191Asn	missense_variant	Exon 2 of 2	1	NM_001010862.3	ENSP00000364054.3
SPIN3	ENST00000639257.1	n.225+346G>A		intron_variant	Intron 2 of 4	3		ENSP00000492259.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1098012 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363376

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000568

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.571G>A (p.D191N) alteration is located in exon 2 (coding exon 1) of the SPIN3 gene. This alteration results from a G to A substitution at nucleotide position 571, causing the aspartic acid (D) at amino acid position 191 to be replaced by an asparagine (N). 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	0.13
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T;T;T;T;T;.;.
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	.;.;.;.;.;.;D;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.29	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.7	L;L;L;L;L;L;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.8	N;.;.;.;.;.;.;.
REVEL	Benign	0.16
Sift	Uncertain	0.0060	D;.;.;.;.;.;.;.
Sift4G	Benign	0.28	T;.;.;.;.;.;.;.
Polyphen		0.048	B;B;B;B;B;B;.;.
Vest4		0.33
MutPred		0.21		Loss of catalytic residue at D191 (P = 0.1094);Loss of catalytic residue at D191 (P = 0.1094);Loss of catalytic residue at D191 (P = 0.1094);Loss of catalytic residue at D191 (P = 0.1094);Loss of catalytic residue at D191 (P = 0.1094);Loss of catalytic residue at D191 (P = 0.1094);.;.;
MVP		0.33
MPC		0.90
ClinPred		0.88	D
GERP RS		2.7
Varity_R		0.18
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs772664485; hg19: chrX-57020810;