Genetic Variant SPIN3:p.Arg46Gln (chrX-56994811-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001010862.3(SPIN3):c.137G>A(p.Arg46Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,209,895 control chromosomes in the GnomAD database, including 1 homozygotes. There are 41 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R46W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.00011 ( 1 hom. 35 hem. )

Consequence

SPIN3
NM_001010862.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.207

Publications

3 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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005130112).

BP6

Variant X-56994811-C-T is Benign according to our data. Variant chrX-56994811-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2660711.Status of the report is criteria_provided_single_submitter, 1 stars.

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.137G>A	p.Arg46Gln	missense	Exon 2 of 2	NP_001010862.2	Q5JUX0-1
	SPIN3	NR_027139.2		n.465G>A		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPIN3	ENST00000374919.6	TSL:1 MANE Select	c.137G>A	p.Arg46Gln	missense	Exon 2 of 2	ENSP00000364054.3	Q5JUX0-1
SPIN3	ENST00000478405.1	TSL:1	n.137G>A		non_coding_transcript_exon	Exon 2 of 5	ENSP00000433337.1	Q5JUX0-2
SPIN3	ENST00000639257.1	TSL:3	n.137G>A		non_coding_transcript_exon	Exon 2 of 5	ENSP00000492259.1	Q5JUX0-2

Frequencies

GnomAD3 genomes

AF:

0.000215

AC:

AN:

111600

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000944

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00593

Gnomad SAS

AF:

0.000767

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000340

AC:

AN:

182121

AF XY:

0.000296

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00394

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000224

GnomAD4 exome

AF:

0.000108

AC:

119

AN:

1098242

Hom.:

Cov.:

AF XY:

0.0000963

AC XY:

AN XY:

363596

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26403

American (AMR)

AF:

0.0000284

AC:

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19385

East Asian (EAS)

AF:

0.00175

AC:

AN:

30204

South Asian (SAS)

AF:

0.000406

AC:

AN:

54143

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40525

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.00000237

AC:

AN:

842142

Other (OTH)

AF:

0.000889

AC:

AN:

46097

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

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:

0.000206

AC:

AN:

111653

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

AN XY:

33853

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30734

American (AMR)

AF:

0.0000943

AC:

AN:

10602

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2645

East Asian (EAS)

AF:

0.00567

AC:

AN:

3530

South Asian (SAS)

AF:

0.000770

AC:

AN:

2598

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6037

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53080

Other (OTH)

AF:

0.00

AC:

AN:

1525

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

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:

0.00

Hom.:

Bravo

AF:

0.000155

ExAC

AF:

0.000272

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.80

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.086

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.83

MetaRNN

Benign

0.0051

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

0.21

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.4

REVEL

Benign

0.054

Sift

Benign

0.30

Sift4G

Benign

0.35

Polyphen

0.0010

Vest4

0.025

MutPred

0.28

Loss of MoRF binding (P = 0.0286)

MVP

0.10

MPC

0.55

ClinPred

0.018

GERP RS

-0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.45

Mutation Taster

=98/2

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