Genetic Variant NM_022117.4:c.272G>C (chrX-53082770-G-C) – 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.272G>C(p.Gly91Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000332 in 1,192,708 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 126 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 0.00021 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.00035 ( 0 hom. 120 hem. )

Consequence

TSPYL2
NM_022117.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.85

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=0.12692916).

BS2

High Hemizygotes in GnomAd4 at 6 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.272G>C	p.Gly91Ala	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.272G>C	p.Gly91Ala	missense	Exon 1 of 7	ENSP00000364591.4	Q9H2G4
TSPYL2	ENST00000912653.1		c.272G>C	p.Gly91Ala	missense	Exon 1 of 7	ENSP00000582712.1
TSPYL2	ENST00000887608.1		c.272G>C	p.Gly91Ala	missense	Exon 1 of 7	ENSP00000557667.1

Frequencies

GnomAD3 genomes

AF:

0.000206

AC:

AN:

111607

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000976

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000376

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000359

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000186

AC:

AN:

145339

AF XY:

0.000143

show subpopulations

Gnomad AFR exome

AF:

0.000203

Gnomad AMR exome

AF:

0.0000892

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000302

Gnomad OTH exome

AF:

0.000278

GnomAD4 exome

AF:

0.000345

AC:

373

AN:

1081101

Hom.:

Cov.:

AF XY:

0.000341

AC XY:

120

AN XY:

352115

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25716

American (AMR)

AF:

0.0000635

AC:

AN:

31483

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18723

East Asian (EAS)

AF:

0.00

AC:

AN:

29761

South Asian (SAS)

AF:

0.000326

AC:

AN:

52192

European-Finnish (FIN)

AF:

0.0000258

AC:

AN:

38770

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4053

European-Non Finnish (NFE)

AF:

0.000404

AC:

337

AN:

835073

Other (OTH)

AF:

0.000353

AC:

AN:

45330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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

100

<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:

111607

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

AN XY:

33825

show subpopulations

African (AFR)

AF:

0.0000976

AC:

AN:

30735

American (AMR)

AF:

0.00

AC:

AN:

10643

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2643

East Asian (EAS)

AF:

0.00

AC:

AN:

3519

South Asian (SAS)

AF:

0.000376

AC:

AN:

2659

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6065

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.000359

AC:

AN:

52925

Other (OTH)

AF:

0.00

AC:

AN:

1502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

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:

0.000521

Hom.:

Bravo

AF:

0.000219

ESP6500AA

AF:

0.000265

AC:

ESP6500EA

AF:

0.000150

AC:

ExAC

AF:

0.000183

AC:

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

0.18

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.33

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.79

M_CAP

Benign

0.029

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

2.9

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.95

REVEL

Benign

0.039

Sift

Uncertain

0.011

Sift4G

Benign

0.36

Polyphen

0.82

Vest4

0.14

MVP

0.17

MPC

0.70

ClinPred

0.041

GERP RS

3.4

PromoterAI

0.011

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.052

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