Genetic Variant TSKU:p.Arg144Trp (chr11-76796046-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015516.4(TSKU):c.430C>T(p.Arg144Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000898 in 1,614,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000090 ( 0 hom. )

Consequence

TSKU
NM_015516.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.794

Publications

2 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.025401562).

BS2

High AC in GnomAd4 at 14 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015516.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSKU	NM_015516.4	MANE Select	c.430C>T	p.Arg144Trp	missense	Exon 2 of 2	NP_056331.2
TSKU	NM_001318477.2		c.472C>T	p.Arg158Trp	missense	Exon 2 of 2	NP_001305406.1
TSKU	NM_001258210.2		c.430C>T	p.Arg144Trp	missense	Exon 2 of 2	NP_001245139.1	Q8WUA8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSKU	ENST00000333090.5	TSL:1 MANE Select	c.430C>T	p.Arg144Trp	missense	Exon 2 of 2	ENSP00000332668.4	Q8WUA8
TSKU	ENST00000527881.1	TSL:2	c.430C>T	p.Arg144Trp	missense	Exon 2 of 2	ENSP00000434847.1	Q8WUA8
TSKU	ENST00000612930.1	TSL:4	c.430C>T	p.Arg144Trp	missense	Exon 2 of 2	ENSP00000482145.1	Q8WUA8

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000167

AC:

AN:

251234

AF XY:

0.000228

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00258

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000896

AC:

131

AN:

1461796

Hom.:

Cov.:

AF XY:

0.000100

AC XY:

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00241

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000371

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53326

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000198

AC:

AN:

1112008

Other (OTH)

AF:

0.000199

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000919

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41576

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000415

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

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:

0.000165

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000173

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

0.089

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.67

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.49

M_CAP

Benign

0.017

MetaRNN

Benign

0.025

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.3

PhyloP100

0.79

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.081

Sift

Benign

0.030

Sift4G

Uncertain

0.027

Polyphen

0.94

Vest4

0.12

MVP

0.082

MPC

0.85

ClinPred

0.12

GERP RS

0.58

Varity_R

0.055

gMVP

0.50

Mutation Taster

=95/5

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