Variant 11-76796100-G-T 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_015516.4(TSKU):c.484G>T(p.Val162Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,613,962 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 14 hom. )

Consequence

TSKU
NM_015516.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.65

Variant links:

Genes affected

TSKU (HGNC:28850): (tsukushi, small leucine rich proteoglycan) Predicted to enable transforming growth factor beta binding activity. Predicted to be involved in several processes, including animal organ development; cholesterol efflux; and cholesterol homeostasis. Predicted to act upstream of or within several processes, including ciliary body morphogenesis; negative regulation of Wnt signaling pathway; and telencephalon development. Predicted to be located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

TSKU 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=0.007963091).

BP6

Variant 11-76796100-G-T is Benign according to our data. Variant chr11-76796100-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1648289.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 271 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSKU	NM_015516.4 linkuse as main transcript	c.484G>T	p.Val162Leu	missense_variant	2/2	ENST00000333090.5	NP_056331.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TSKU	ENST00000333090.5 linkuse as main transcript	c.484G>T	p.Val162Leu	missense_variant	2/2	1	NM_015516.4	ENSP00000332668	P1
TSKU	ENST00000527881.1 linkuse as main transcript	c.484G>T	p.Val162Leu	missense_variant	2/2	2		ENSP00000434847	P1
TSKU	ENST00000612930.1 linkuse as main transcript	c.484G>T	p.Val162Leu	missense_variant	2/2	4		ENSP00000482145	P1
TSKU	ENST00000533752.1 linkuse as main transcript			downstream_gene_variant		4		ENSP00000435133

Frequencies

GnomAD3 genomes

AF:

0.00179

AC:

272

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00343

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00216

AC:

542

AN:

251070

Hom.:

AF XY:

0.00231

AC XY:

314

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00229

Gnomad FIN exome

AF:

0.000974

Gnomad NFE exome

AF:

0.00351

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00266

AC:

3894

AN:

1461776

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

1940

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.000648

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00210

Gnomad4 FIN exome

AF:

0.00122

Gnomad4 NFE exome

AF:

0.00309

Gnomad4 OTH exome

AF:

0.00268

GnomAD4 genome

AF:

0.00178

AC:

271

AN:

152186

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

114

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00146

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00341

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00269

Hom.:

Bravo

AF:

0.00159

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00349

AC:

ExAC

AF:

0.00287

AC:

349

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00213

EpiControl

AF:

0.00172

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

Jun 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.10

T;T;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.81

T;.;.

M_CAP

Benign

0.0090

MetaRNN

Benign

0.0080

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.8

L;L;L

MutationTaster

Benign

0.85

D;D

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-0.16

.;N;N

REVEL

Benign

0.048

Sift

Benign

0.20

.;T;T

Sift4G

Benign

0.54

T;T;T

Polyphen

0.20

B;B;B

Vest4

0.23

MutPred

0.80

Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);

MVP

0.068

MPC

0.39

ClinPred

0.0052

GERP RS

2.1

Varity_R

0.033

gMVP

0.48

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