Variant X-56994388-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001010862.3(SPIN3):c.560G>A(p.Arg187His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,209,241 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000039 ( 0 hom. 11 hem. )

Consequence

SPIN3
NM_001010862.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.09

Variant links:

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]

SPIN3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06352854).

BS2

High Hemizygotes in GnomAdExome4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPIN3	NM_001010862.3 linkuse as main transcript	c.560G>A	p.Arg187His	missense_variant	2/2	ENST00000374919.6	NP_001010862.2	Q5JUX0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPIN3	ENST00000374919.6 linkuse as main transcript	c.560G>A	p.Arg187His	missense_variant	2/2	1	NM_001010862.3	ENSP00000364054.3		Q5JUX0-1
SPIN3	ENST00000639257.1 linkuse as main transcript	n.225+335G>A		intron_variant		3		ENSP00000492259.1		Q5JUX0-2

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111501

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33689

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000378

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000771

AC:

AN:

181635

Hom.:

AF XY:

0.0000893

AC XY:

AN XY:

67159

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.00134

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000246

Gnomad OTH exome

AF:

0.000224

GnomAD4 exome

AF:

0.0000392

AC:

AN:

1097687

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

363055

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00114

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000178

Gnomad4 OTH exome

AF:

0.000109

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111554

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33752

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000378

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000260

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000825

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2023

The c.560G>A (p.R187H) 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 560, causing the arginine (R) at amino acid position 187 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

0.068

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.34

DEOGEN2

Benign

0.18

T;T;T;T;T;T;.;.

FATHMM_MKL

Benign

0.52

LIST_S2

Uncertain

0.90

.;.;.;.;.;.;D;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.064

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.65

N;N;N;N;N;N;.;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.2

N;.;.;.;.;.;.;.

REVEL

Benign

0.10

Sift

Benign

0.54

T;.;.;.;.;.;.;.

Sift4G

Benign

0.45

T;.;.;.;.;.;.;.

Polyphen

0.049

B;B;B;B;B;B;.;.

Vest4

0.17

MutPred

0.44

Gain of catalytic residue at L189 (P = 0.0819);Gain of catalytic residue at L189 (P = 0.0819);Gain of catalytic residue at L189 (P = 0.0819);Gain of catalytic residue at L189 (P = 0.0819);Gain of catalytic residue at L189 (P = 0.0819);Gain of catalytic residue at L189 (P = 0.0819);.;.;

MVP

0.11

MPC

0.59

ClinPred

0.024

GERP RS

-1.6

Varity_R

0.17

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over