Genetic Variant TSKU:p.Thr153Lys (chr11-76796074-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015516.4(TSKU):c.458C>A(p.Thr153Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T153M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TSKU
NM_015516.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.01

Publications

3 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21446869).

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.458C>A	p.Thr153Lys	missense	Exon 2 of 2	NP_056331.2
TSKU	NM_001318477.2		c.500C>A	p.Thr167Lys	missense	Exon 2 of 2	NP_001305406.1
TSKU	NM_001258210.2		c.458C>A	p.Thr153Lys	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.458C>A	p.Thr153Lys	missense	Exon 2 of 2	ENSP00000332668.4	Q8WUA8
TSKU	ENST00000527881.1	TSL:2	c.458C>A	p.Thr153Lys	missense	Exon 2 of 2	ENSP00000434847.1	Q8WUA8
TSKU	ENST00000612930.1	TSL:4	c.458C>A	p.Thr153Lys	missense	Exon 2 of 2	ENSP00000482145.1	Q8WUA8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251124

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

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:

6.84e-7

AC:

AN:

1461810

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60396

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

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

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.14

Eigen

Benign

0.18

Eigen_PC

Benign

0.088

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.70

M_CAP

Benign

0.011

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

5.0

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.82

REVEL

Benign

0.15

Sift

Benign

0.089

Sift4G

Benign

0.88

Polyphen

0.94

Vest4

0.16

MutPred

0.44

Gain of ubiquitination at T153 (P = 0.0247)

MVP

0.068

MPC

0.94

ClinPred

0.44

GERP RS

5.2

Varity_R

0.057

gMVP

0.38

Mutation Taster

=81/19

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over