Genetic Variant TEKTL1:p.Pro102Ser (chr19-15011129-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_173482.3(TEKTL1):c.304C>T(p.Pro102Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000457 in 1,533,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

TEKTL1
NM_173482.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78

Publications

0 publications found

Variant links:

Genes affected

TEKTL1 (HGNC:26866): (tektin like 1) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

TEKTL1 links:

SLC1A6 (HGNC:10944): (solute carrier family 1 member 6) Predicted to enable high-affinity glutamate transmembrane transporter activity. Involved in neurotransmitter uptake. Located in intermediate filament cytoskeleton and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC1A6 links:

ENSG00000302149 (HGNC:):

ENSG00000302149 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19968194).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173482.3. 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
	TEKTL1	NM_173482.3	MANE Select	c.304C>T	p.Pro102Ser	missense	Exon 1 of 7	NP_775753.2	Q8IYK2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TEKTL1	ENST00000292574.4	TSL:1 MANE Select	c.304C>T	p.Pro102Ser	missense	Exon 1 of 7	ENSP00000292574.2	Q8IYK2
SLC1A6	ENST00000595863.1	TSL:3	c.-8+11775G>A		intron	N/A	ENSP00000469551.1	M0QY32
ENSG00000302149	ENST00000784685.1		n.341-16897G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000240

AC:

AN:

124916

AF XY:

0.0000292

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000301

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000290

AC:

AN:

1381210

Hom.:

Cov.:

AF XY:

0.00000440

AC XY:

AN XY:

681678

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30814

American (AMR)

AF:

0.00

AC:

AN:

32268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24000

East Asian (EAS)

AF:

0.0000834

AC:

AN:

35954

South Asian (SAS)

AF:

0.00

AC:

AN:

77114

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42446

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4680

European-Non Finnish (NFE)

AF:

9.29e-7

AC:

AN:

1076666

Other (OTH)

AF:

0.00

AC:

AN:

57268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

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:

0.0000197

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000578

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2094

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

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:

0.00

Hom.:

Bravo

AF:

0.0000227

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

0.31

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.65

M_CAP

Benign

0.014

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PhyloP100

1.8

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.8

REVEL

Benign

0.098

Sift

Benign

0.16

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.36

MutPred

0.33

Loss of catalytic residue at P102 (P = 0.0045)

MVP

0.40

MPC

1.0

ClinPred

0.56

GERP RS

2.9

PromoterAI

0.00080

Neutral

(source)

Varity_R

0.070

gMVP

0.29

Mutation Taster

=98/2

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

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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