X-56994916-C-T

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

1
16

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]

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
SPIN3NM_001010862.3 linkc.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
SPIN3ENST00000374919.6 linkc.32G>A p.Gly11Glu missense_variant Exon 2 of 2 1 NM_001010862.3 ENSP00000364054.3 Q5JUX0-1
SPIN3ENST00000639257.1 linkn.32G>A non_coding_transcript_exon_variant Exon 2 of 5 3 ENSP00000492259.1 Q5JUX0-2

Frequencies

GnomAD3 genomes
AF:
0.0000178
AC:
2
AN:
112084
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
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:
2
AN:
165643
Hom.:
0
AF XY:
0.00
AC XY:
0
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:
11
AN:
1084631
Hom.:
0
Cov.:
31
AF XY:
0.0000113
AC XY:
4
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:
2
AN:
112084
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
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:
0
ESP6500EA
AF:
0.000306
AC:
2
ExAC
AF:
0.00000826
AC:
1

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
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
16
DANN
Benign
0.74
DEOGEN2
Benign
0.053
T;T;T;T;.;T;T;.;.;.
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.62
.;.;.;.;T;.;.;T;T;T
M_CAP
Benign
0.068
D
MetaRNN
Benign
0.10
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
L;L;L;L;.;L;L;.;.;.
PrimateAI
Uncertain
0.58
T
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
T
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.

Other links and lift over

dbSNP: rs377082003; hg19: chrX-57021349; API