Variant 8-97277438-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_033512.3(TSPYL5):c.407C>T(p.Pro136Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00423 in 1,546,190 control chromosomes in the GnomAD database, including 19 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 17 hom. )

Consequence

TSPYL5
NM_033512.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.11

Variant links:

Genes affected

TSPYL5 (HGNC:29367): (TSPY like 5) Predicted to enable chromatin binding activity and histone binding activity. Involved in several processes, including cellular response to gamma radiation; positive regulation of protein kinase B signaling; and positive regulation of protein ubiquitination. Predicted to be active in chromatin and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TSPYL5 links:

LOC101927066 (HGNC:):

LOC101927066 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004634261).

BP6

Variant 8-97277438-G-A is Benign according to our data. Variant chr8-97277438-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 783011.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPYL5	NM_033512.3 linkuse as main transcript	c.407C>T	p.Pro136Leu	missense_variant	1/1	ENST00000322128.5	NP_277047.2
LOC101927066	NR_125390.1 linkuse as main transcript	n.471+141632C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPYL5	ENST00000322128.5 linkuse as main transcript	c.407C>T	p.Pro136Leu	missense_variant	1/1		NM_033512.3	ENSP00000322802	P1

Frequencies

GnomAD3 genomes

AF:

0.00292

AC:

445

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0101

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00437

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00284

AC:

533

AN:

187530

Hom.:

AF XY:

0.00284

AC XY:

284

AN XY:

99964

show subpopulations

Gnomad AFR exome

AF:

0.000627

Gnomad AMR exome

AF:

0.000682

Gnomad ASJ exome

AF:

0.000225

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000117

Gnomad FIN exome

AF:

0.00906

Gnomad NFE exome

AF:

0.00371

Gnomad OTH exome

AF:

0.00211

GnomAD4 exome

AF:

0.00437

AC:

6088

AN:

1393868

Hom.:

Cov.:

AF XY:

0.00423

AC XY:

2911

AN XY:

687652

show subpopulations

Gnomad4 AFR exome

AF:

0.000810

Gnomad4 AMR exome

AF:

0.000588

Gnomad4 ASJ exome

AF:

0.000237

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.0000678

Gnomad4 FIN exome

AF:

0.00963

Gnomad4 NFE exome

AF:

0.00493

Gnomad4 OTH exome

AF:

0.00358

GnomAD4 genome

AF:

0.00292

AC:

445

AN:

152322

Hom.:

Cov.:

AF XY:

0.00302

AC XY:

225

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0101

Gnomad4 NFE

AF:

0.00437

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00387

Hom.:

Bravo

AF:

0.00227

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.000683

AC:

ESP6500EA

AF:

0.00408

AC:

ExAC

AF:

0.00231

AC:

280

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 13, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0072

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.62

M_CAP

Benign

0.0034

MetaRNN

Benign

0.0046

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

0.96

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-2.0

REVEL

Benign

0.044

Sift

Benign

0.66

Sift4G

Benign

0.55

Polyphen

0.031

Vest4

0.15

MVP

0.043

MPC

0.94

ClinPred

0.022

GERP RS

4.3

Varity_R

0.079

gMVP

0.094

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over