Genetic Variant SPIN3:p.Lys242Thr (chrX-56994223-T-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001010862.3(SPIN3):c.725A>C(p.Lys242Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000497 in 1,206,609 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K242R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0000046 ( 0 hom. 1 hem. )

Consequence

SPIN3
NM_001010862.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.28

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.793

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.725A>C	p.Lys242Thr	missense	Exon 2 of 2	NP_001010862.2	Q5JUX0-1
	SPIN3	NR_027139.2		n.553+500A>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPIN3	ENST00000374919.6	TSL:1 MANE Select	c.725A>C	p.Lys242Thr	missense	Exon 2 of 2	ENSP00000364054.3	Q5JUX0-1
SPIN3	ENST00000478405.1	TSL:1	n.225+500A>C		intron	N/A	ENSP00000433337.1	Q5JUX0-2
SPIN3	ENST00000639257.1	TSL:3	n.225+500A>C		intron	N/A	ENSP00000492259.1	Q5JUX0-2

Frequencies

GnomAD3 genomes

AF:

0.00000894

AC:

AN:

111840

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000457

AC:

AN:

1094769

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

360539

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26286

American (AMR)

AF:

0.00

AC:

AN:

34518

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19188

East Asian (EAS)

AF:

0.00

AC:

AN:

30176

South Asian (SAS)

AF:

0.00

AC:

AN:

53071

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40507

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4110

European-Non Finnish (NFE)

AF:

0.00000476

AC:

AN:

840926

Other (OTH)

AF:

0.0000217

AC:

AN:

45987

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.00000894

AC:

AN:

111840

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

34012

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30728

American (AMR)

AF:

0.00

AC:

AN:

10592

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3560

South Asian (SAS)

AF:

0.00

AC:

AN:

2662

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6048

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53181

Other (OTH)

AF:

0.00

AC:

AN:

1493

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.044

MetaRNN

Pathogenic

0.79

MetaSVM

Benign

-0.45

MutationAssessor

Uncertain

2.6

PhyloP100

6.3

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.35

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.70

MutPred

0.67

Loss of methylation at K242 (P = 0.0011)

MVP

0.52

MPC

1.5

ClinPred

1.0

GERP RS

2.7

Varity_R

0.84

gMVP

0.66

Mutation Taster

=48/52

disease causing

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over