dbSNP rs200340428: SPIN3:p.Val232Leu (chrX-56994254-C-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -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

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

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

BS2

High Hemizygotes in GnomAd4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010862.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPIN3	NM_001010862.3	MANE Select	c.694G>T	p.Val232Leu	missense	Exon 2 of 2	NP_001010862.2	Q5JUX0-1
	SPIN3	NR_027139.2		n.553+469G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPIN3	ENST00000374919.6	TSL:1 MANE Select	c.694G>T	p.Val232Leu	missense	Exon 2 of 2	ENSP00000364054.3	Q5JUX0-1
SPIN3	ENST00000478405.1	TSL:1	n.225+469G>T		intron	N/A	ENSP00000433337.1	Q5JUX0-2
SPIN3	ENST00000639257.1	TSL:3	n.225+469G>T		intron	N/A	ENSP00000492259.1	Q5JUX0-2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

111806

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000170

AC:

AN:

182521

AF XY:

0.000207

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 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

African (AFR)

AF:

0.0000379

AC:

AN:

26402

American (AMR)

AF:

0.00

AC:

AN:

35198

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19384

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.00

AC:

AN:

54116

European-Finnish (FIN)

AF:

0.0000987

AC:

AN:

40532

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.000166

AC:

140

AN:

842040

Other (OTH)

AF:

0.000195

AC:

AN:

46092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000125

AC:

AN:

111806

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

AN XY:

33972

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30734

American (AMR)

AF:

0.00

AC:

AN:

10599

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2656

East Asian (EAS)

AF:

0.00

AC:

AN:

3549

South Asian (SAS)

AF:

0.00

AC:

AN:

2646

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6033

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.000263

AC:

AN:

53163

Other (OTH)

AF:

0.00

AC:

AN:

1505

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.556

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000132

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.36

MutationAssessor

Uncertain

2.6

PhyloP100

6.1

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.31

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.013

Polyphen

1.0

Vest4

0.63

MutPred

0.76

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

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over