Variant X-56994254-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001010862.3(SPIN3):c.694G>T(p.Val232Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00014 in 1,209,912 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 61 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.00014 ( 0 hom. 55 hem. )

Consequence

SPIN3
NM_001010862.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.13

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3071554).

BS2

High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPIN3	NM_001010862.3 linkuse as main transcript	c.694G>T	p.Val232Leu	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.694G>T	p.Val232Leu	missense_variant	2/2	1	NM_001010862.3	ENSP00000364054.3		Q5JUX0-1
SPIN3	ENST00000639257.1 linkuse as main transcript	n.225+469G>T		intron_variant		3		ENSP00000492259.1		Q5JUX0-2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

111806

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

AN XY:

33972

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:

0.000263

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000170

AC:

AN:

182521

Hom.:

AF XY:

0.000207

AC XY:

AN XY:

67567

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:

0.000188

Gnomad NFE exome

AF:

0.000331

Gnomad OTH exome

AF:

0.000223

GnomAD4 exome

AF:

0.000141

AC:

155

AN:

1098106

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

AN XY:

363460

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

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:

0.0000987

Gnomad4 NFE exome

AF:

0.000166

Gnomad4 OTH exome

AF:

0.000195

GnomAD4 genome

AF:

0.000125

AC:

AN:

111806

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

AN XY:

33972

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:

0.000263

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000143

Hom.:

Bravo

AF:

0.000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000198

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000296

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

Aug 05, 2024

The c.694G>T (p.V232L) alteration is located in exon 2 (coding exon 1) of the SPIN3 gene. This alteration results from a G to T substitution at nucleotide position 694, causing the valine (V) at amino acid position 232 to be replaced by a leucine (L). 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

0.92

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

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

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

.;.;.;.;.;.;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.31

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

MetaSVM

Benign

-0.36

MutationAssessor

Uncertain

2.6

M;M;M;M;M;M;.

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.2

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

REVEL

Uncertain

0.31

Sift

Uncertain

0.0030

D;.;.;.;.;.;.

Sift4G

Uncertain

0.013

D;.;.;.;.;.;.

Polyphen

1.0

D;D;D;D;D;D;.

Vest4

0.63

MutPred

0.76

Gain of catalytic residue at V232 (P = 0.0784);Gain of catalytic residue at V232 (P = 0.0784);Gain of catalytic residue at V232 (P = 0.0784);Gain of catalytic residue at V232 (P = 0.0784);Gain of catalytic residue at V232 (P = 0.0784);Gain of catalytic residue at V232 (P = 0.0784);.;

MVP

0.64

MPC

1.4

ClinPred

0.24

GERP RS

2.7

Varity_R

0.69

gMVP

0.83

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