Variant X-56994751-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001010862.3(SPIN3):c.197C>T(p.Thr66Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00023 in 1,210,244 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 85 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000071 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.00025 ( 0 hom. 81 hem. )

Consequence

SPIN3
NM_001010862.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.91

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=0.13238537).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPIN3	NM_001010862.3 linkuse as main transcript	c.197C>T	p.Thr66Ile	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.197C>T	p.Thr66Ile	missense_variant	2/2	1	NM_001010862.3	ENSP00000364054.3		Q5JUX0-1
SPIN3	ENST00000639257.1 linkuse as main transcript	n.197C>T		non_coding_transcript_exon_variant	2/5	3		ENSP00000492259.1		Q5JUX0-2

Frequencies

GnomAD3 genomes

AF:

0.0000714

AC:

AN:

112038

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34204

show subpopulations

Gnomad AFR

AF:

0.0000649

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:

0.000113

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000658

AC:

AN:

182351

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

67533

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

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:

0.000135

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000246

AC:

270

AN:

1098154

Hom.:

Cov.:

AF XY:

0.000223

AC XY:

AN XY:

363508

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.0000284

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:

0.000309

Gnomad4 OTH exome

AF:

0.000174

GnomAD4 genome

AF:

0.0000714

AC:

AN:

112090

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34266

show subpopulations

Gnomad4 AFR

AF:

0.0000648

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:

0.000113

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000260

Hom.:

Bravo

AF:

0.0000529

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000298

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Oct 24, 2024

The c.197C>T (p.T66I) alteration is located in exon 2 (coding exon 1) of the SPIN3 gene. This alteration results from a C to T substitution at nucleotide position 197, causing the threonine (T) at amino acid position 66 to be replaced by an isoleucine (I). 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

0.32

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.22

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

FATHMM_MKL

Benign

0.48

LIST_S2

Uncertain

0.86

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

M_CAP

Benign

0.063

MetaRNN

Benign

0.13

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

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.7

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

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-4.4

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

REVEL

Benign

0.12

Sift

Uncertain

0.014

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

Sift4G

Uncertain

0.021

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

Polyphen

0.0020

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

Vest4

0.50

MVP

0.12

MPC

0.52

ClinPred

0.13

GERP RS

-0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.50

gMVP

0.50

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