Genetic Variant TASL:p.Cys121Phe (chrX-30559994-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_025159.3(TASL):c.362G>T(p.Cys121Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000561 in 1,209,292 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 218 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., 18 hem., cov: 22)

Exomes 𝑓: 0.00056 ( 0 hom. 200 hem. )

Consequence

TASL
NM_025159.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.46

Publications

0 publications found

Variant links:

Genes affected

TASL (HGNC:25667): (TLR adaptor interacting with endolysosomal SLC15A4) Involved in positive regulation of innate immune response; positive regulation of toll-like receptor signaling pathway; and regulation of lysosomal lumen pH. Located in endolysosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

TASL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 18 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025159.3. 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
	TASL	NM_025159.3	MANE Select	c.362G>T	p.Cys121Phe	missense	Exon 3 of 3	NP_079435.1	Q9HAI6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TASL	ENST00000378962.4	TSL:1 MANE Select	c.362G>T	p.Cys121Phe	missense	Exon 3 of 3	ENSP00000368245.3	Q9HAI6
TASL	ENST00000955826.1		c.362G>T	p.Cys121Phe	missense	Exon 3 of 3	ENSP00000625885.1
TASL	ENST00000955827.1		c.362G>T	p.Cys121Phe	missense	Exon 2 of 2	ENSP00000625886.1

Frequencies

GnomAD3 genomes

AF:

0.000599

AC:

AN:

111913

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000650

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000164

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00115

Gnomad OTH

AF:

0.00200

GnomAD2 exomes

AF:

0.000354

AC:

AN:

180912

AF XY:

0.000393

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.000257

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000673

Gnomad OTH exome

AF:

0.000223

GnomAD4 exome

AF:

0.000558

AC:

612

AN:

1097379

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

200

AN XY:

362751

show subpopulations

African (AFR)

AF:

0.000152

AC:

AN:

26381

American (AMR)

AF:

0.000284

AC:

AN:

35159

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19352

East Asian (EAS)

AF:

0.00

AC:

AN:

30204

South Asian (SAS)

AF:

0.00

AC:

AN:

54006

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40482

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.000687

AC:

578

AN:

841608

Other (OTH)

AF:

0.000434

AC:

AN:

46057

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

108

135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000599

AC:

AN:

111913

Hom.:

Cov.:

AF XY:

0.000528

AC XY:

AN XY:

34061

show subpopulations

African (AFR)

AF:

0.0000650

AC:

AN:

30776

American (AMR)

AF:

0.00

AC:

AN:

10518

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3564

South Asian (SAS)

AF:

0.00

AC:

AN:

2663

European-Finnish (FIN)

AF:

0.000164

AC:

AN:

6091

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.00115

AC:

AN:

53220

Other (OTH)

AF:

0.00200

AC:

AN:

1499

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000636

Hom.:

Bravo

AF:

0.000559

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.000239

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.000475

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

0.24

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Pathogenic

0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.81

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.67

MetaSVM

Uncertain

-0.21

MutationAssessor

Uncertain

2.6

PhyloP100

4.5

PROVEAN

Pathogenic

-7.3

REVEL

Uncertain

0.56

Sift

Uncertain

0.023

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.76

MVP

0.85

MPC

1.0

ClinPred

0.23

GERP RS

4.2

Varity_R

0.89

gMVP

0.71

Mutation Taster

=78/22

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