Genetic Variant SPIN2B:p.Thr66Met (chrX-57120433-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001006681.2(SPIN2B):c.197C>T(p.Thr66Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., 0 hem., cov: 7)

Exomes 𝑓: 0.0000025 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

SPIN2B
NM_001006681.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.91

Variant links:

Genes affected

SPIN2B (HGNC:33147): (spindlin family member 2B) Enables methylated histone binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SPIN2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPIN2B	NM_001006681.2 link	c.197C>T	p.Thr66Met	missense_variant	Exon 2 of 2	ENST00000434397.3	NP_001006682.1	Q9BPZ2A0A024R9Y9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPIN2B	ENST00000434397.3 link	c.197C>T	p.Thr66Met	missense_variant	Exon 2 of 2	1	NM_001006681.2	ENSP00000404314.2		Q9BPZ2Q5JZB8

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

50963

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

2253

FAILED QC

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000249

AC:

AN:

803398

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

202270

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:

0.0000236

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000170

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

50963

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

2253

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:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.197C>T (p.T66M) alteration is located in exon 2 (coding exon 1) of the SPIN2B 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 a methionine (M). 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

0.29

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

.;.;T;T;.

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.55

T;T;.;T;T

M_CAP

Benign

0.0055

MetaRNN

Uncertain

0.46

T;T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

2.0

.;.;M;M;.

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-4.2

.;D;D;D;D

REVEL

Benign

0.21

Sift

Benign

0.042

.;D;D;D;D

Sift4G

Uncertain

0.014

.;D;D;D;.

Polyphen

1.0

.;.;D;D;.

Vest4

0.21, 0.27

MutPred

0.49

.;Loss of ubiquitination at K69 (P = 0.0613);Loss of ubiquitination at K69 (P = 0.0613);Loss of ubiquitination at K69 (P = 0.0613);Loss of ubiquitination at K69 (P = 0.0613);

MVP

0.36

MPC

3.1

ClinPred

0.98

GERP RS

1.5

Varity_R

0.47

gMVP

0.37

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over