Genetic Variant NM_022117.4:c.89C>T (chrX-53082587-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_022117.4(TSPYL2):c.89C>T(p.Pro30Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,151,302 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000013 ( 0 hom. 7 hem. )

Consequence

TSPYL2
NM_022117.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.60

Publications

0 publications found

Variant links:

Genes affected

TSPYL2 (HGNC:24358): (TSPY like 2) This gene encodes a member of the testis-specific protein Y-encoded, TSPY-like/SET/nucleosome assembly protein-1 superfamily. The encoded protein is localized to the nucleolus where it functions in chromatin remodeling and as an inhibitor of cell-cycle progression. This protein may play a role in the suppression of tumor growth. [provided by RefSeq, Sep 2009]

TSPYL2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16235587).

BS2

High Hemizygotes in GnomAdExome4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022117.4. 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
	TSPYL2	NM_022117.4	MANE Select	c.89C>T	p.Pro30Leu	missense	Exon 1 of 7	NP_071400.1	Q9H2G4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSPYL2	ENST00000375442.8	TSL:1 MANE Select	c.89C>T	p.Pro30Leu	missense	Exon 1 of 7	ENSP00000364591.4	Q9H2G4
TSPYL2	ENST00000912653.1		c.89C>T	p.Pro30Leu	missense	Exon 1 of 7	ENSP00000582712.1
TSPYL2	ENST00000887608.1		c.89C>T	p.Pro30Leu	missense	Exon 1 of 7	ENSP00000557667.1

Frequencies

GnomAD3 genomes

AF:

0.00000897

AC:

AN:

111471

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000936

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

GnomAD2 exomes

AF:

0.0000448

AC:

AN:

89308

AF XY:

0.0000645

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000162

Gnomad ASJ exome

AF:

0.000182

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000135

AC:

AN:

1039831

Hom.:

Cov.:

AF XY:

0.0000207

AC XY:

AN XY:

338561

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24407

American (AMR)

AF:

0.000110

AC:

AN:

27373

Ashkenazi Jewish (ASJ)

AF:

0.000328

AC:

AN:

18287

East Asian (EAS)

AF:

0.00

AC:

AN:

26815

South Asian (SAS)

AF:

0.00

AC:

AN:

49347

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29355

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3088

European-Non Finnish (NFE)

AF:

0.00000367

AC:

AN:

817164

Other (OTH)

AF:

0.0000455

AC:

AN:

43995

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.00000897

AC:

AN:

111471

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33807

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30677

American (AMR)

AF:

0.0000936

AC:

AN:

10683

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3504

South Asian (SAS)

AF:

0.00

AC:

AN:

2735

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5971

Middle Eastern (MID)

AF:

0.00

AC:

AN:

233

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52847

Other (OTH)

AF:

0.00

AC:

AN:

1495

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000113

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

Benign

0.14

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.68

M_CAP

Pathogenic

0.41

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.59

MutationAssessor

Benign

0.69

PhyloP100

2.6

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.0

REVEL

Benign

0.16

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

0.046

Vest4

0.31

MutPred

0.25

Loss of glycosylation at P30 (P = 5e-04)

MVP

0.54

MPC

0.28

ClinPred

0.072

GERP RS

2.3

PromoterAI

-0.071

Neutral

(source)

Varity_R

0.10

gMVP

0.23

Mutation Taster

=100/0

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