Genetic Variant SPIN3:p.Gly11Glu (chrX-56994916-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001010862.3(SPIN3):c.32G>A(p.Gly11Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,196,715 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 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., 0 hem., cov: 23)

Exomes 𝑓: 0.000010 ( 0 hom. 4 hem. )

Consequence

SPIN3
NM_001010862.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.137

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.101523966).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPIN3	NM_001010862.3 link	c.32G>A	p.Gly11Glu	missense_variant	Exon 2 of 2	ENST00000374919.6	NP_001010862.2	Q5JUX0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPIN3	ENST00000374919.6 link	c.32G>A	p.Gly11Glu	missense_variant	Exon 2 of 2	1	NM_001010862.3	ENSP00000364054.3		Q5JUX0-1
SPIN3	ENST00000639257.1 link	n.32G>A		non_coding_transcript_exon_variant	Exon 2 of 5	3		ENSP00000492259.1		Q5JUX0-2

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112084

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34274

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

165643

Hom.:

AF XY:

0.00

AC XY:

AN XY:

54533

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000101

AC:

AN:

1084631

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

352483

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000132

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112084

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34274

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000306

AC:

ExAC

AF:

0.00000826

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 29, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.32G>A (p.G11E) 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 32, causing the glycine (G) at amino acid position 11 to be replaced by a glutamic acid (E). 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

0.093

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.053

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

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.62

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

M_CAP

Benign

0.068

MetaRNN

Benign

0.10

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L;L;L;.;L;L;.;.;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.34

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

REVEL

Benign

0.012

Sift

Benign

0.14

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

Sift4G

Benign

0.90

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

Polyphen

0.0090

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

Vest4

0.14

MVP

0.10

MPC

0.62

ClinPred

0.036

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.087

gMVP

0.12

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

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