Variant X-30559994-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -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

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 18 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TASL	NM_025159.3 linkuse as main transcript	c.362G>T	p.Cys121Phe	missense_variant	3/3	ENST00000378962.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TASL	ENST00000378962.4 linkuse as main transcript	c.362G>T	p.Cys121Phe	missense_variant	3/3	1	NM_025159.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000599

AC:

AN:

111913

Hom.:

Cov.:

AF XY:

0.000528

AC XY:

AN XY:

34061

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

GnomAD3 exomes

AF:

0.000354

AC:

AN:

180912

Hom.:

AF XY:

0.000393

AC XY:

AN XY:

66146

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 SAS 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

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000687

Gnomad4 OTH exome

AF:

0.000434

GnomAD4 genome

AF:

0.000599

AC:

AN:

111913

Hom.:

Cov.:

AF XY:

0.000528

AC XY:

AN XY:

34061

show subpopulations

Gnomad4 AFR

AF:

0.0000650

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000164

Gnomad4 NFE

AF:

0.00115

Gnomad4 OTH

AF:

0.00200

Alfa

AF:

0.000689

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.362G>T (p.C121F) alteration is located in exon 3 (coding exon 1) of the CXorf21 gene. This alteration results from a G to T substitution at nucleotide position 362, causing the cysteine (C) at amino acid position 121 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Pathogenic

0.43

CADD

Benign

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

MutationTaster

Benign

1.0

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

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