Variant X-56994851-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.97G>A(p.Ala33Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000306 in 1,210,067 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 128 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 0.00026 ( 0 hom., 12 hem., cov: 23)

Exomes 𝑓: 0.00031 ( 0 hom. 116 hem. )

Consequence

SPIN3
NM_001010862.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.457

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=0.06659812).

BS2

High Hemizygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPIN3	NM_001010862.3 linkuse as main transcript	c.97G>A	p.Ala33Thr	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.97G>A	p.Ala33Thr	missense_variant	2/2	1	NM_001010862.3	ENSP00000364054.3		Q5JUX0-1
SPIN3	ENST00000639257.1 linkuse as main transcript	n.97G>A		non_coding_transcript_exon_variant	2/5	3		ENSP00000492259.1		Q5JUX0-2

Frequencies

GnomAD3 genomes

AF:

0.000259

AC:

AN:

111879

Hom.:

Cov.:

AF XY:

0.000353

AC XY:

AN XY:

34039

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:

0.000165

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000508

Gnomad OTH

AF:

0.000668

GnomAD3 exomes

AF:

0.000121

AC:

AN:

181684

Hom.:

AF XY:

0.0000742

AC XY:

AN XY:

67420

show subpopulations

Gnomad AFR exome

AF:

0.0000805

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:

0.0000629

Gnomad NFE exome

AF:

0.000246

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000311

AC:

341

AN:

1098188

Hom.:

Cov.:

AF XY:

0.000319

AC XY:

116

AN XY:

363542

show subpopulations

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:

0.0000369

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.000379

Gnomad4 OTH exome

AF:

0.000260

GnomAD4 genome

AF:

0.000259

AC:

AN:

111879

Hom.:

Cov.:

AF XY:

0.000353

AC XY:

AN XY:

34039

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:

0.000165

Gnomad4 NFE

AF:

0.000508

Gnomad4 OTH

AF:

0.000668

Alfa

AF:

0.000347

Hom.:

Bravo

AF:

0.000200

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.000271

AC:

ESP6500EA

AF:

0.000151

AC:

ExAC

AF:

0.000149

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000415

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

Mar 01, 2024

The c.97G>A (p.A33T) 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 97, causing the alanine (A) at amino acid position 33 to be replaced by a threonine (T). 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

0.073

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.93

CADD

Benign

7.6

DANN

Benign

0.75

DEOGEN2

Benign

0.038

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

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.78

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

M_CAP

Benign

0.0049

MetaRNN

Benign

0.067

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

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

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.27

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

REVEL

Benign

0.033

Sift

Benign

0.61

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

Sift4G

Benign

0.76

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

Polyphen

0.0020

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

Vest4

0.084

MVP

0.12

MPC

0.46

ClinPred

0.038

GERP RS

-2.5

Varity_R

0.063

gMVP

0.28

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