Variant 4-153555894-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001131007.2(TMEM131L):c.416C>T(p.Pro139Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,551,154 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0022 ( 5 hom. )

Consequence

TMEM131L
NM_001131007.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.85

Variant links:

Genes affected

TMEM131L (HGNC:29146): (transmembrane 131 like) Involved in negative regulation of canonical Wnt signaling pathway and negative regulation of immature T cell proliferation in thymus. Located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM131L links:

TMEM131L (HGNC:):

TMEM131L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013923287).

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM131L	NM_001131007.2 linkuse as main transcript	c.416C>T	p.Pro139Leu	missense_variant	5/35	ENST00000409959.8	NP_001124479.1	A2VDJ0-5B3KU55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM131L	ENST00000409959.8 linkuse as main transcript	c.416C>T	p.Pro139Leu	missense_variant	5/35	5	NM_001131007.2	ENSP00000386787.3		A2VDJ0-5

Frequencies

GnomAD3 genomes

AF:

0.00132

AC:

200

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000387

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000852

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000945

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00223

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00134

AC:

210

AN:

156544

Hom.:

AF XY:

0.00131

AC XY:

109

AN XY:

82942

show subpopulations

Gnomad AFR exome

AF:

0.000252

Gnomad AMR exome

AF:

0.000488

Gnomad ASJ exome

AF:

0.000588

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000395

Gnomad FIN exome

AF:

0.000713

Gnomad NFE exome

AF:

0.00272

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00220

AC:

3073

AN:

1399030

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

1398

AN XY:

690048

show subpopulations

Gnomad4 AFR exome

AF:

0.000443

Gnomad4 AMR exome

AF:

0.000729

Gnomad4 ASJ exome

AF:

0.000397

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.000202

Gnomad4 FIN exome

AF:

0.00136

Gnomad4 NFE exome

AF:

0.00263

Gnomad4 OTH exome

AF:

0.00167

GnomAD4 genome

AF:

0.00131

AC:

200

AN:

152124

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.000386

Gnomad4 AMR

AF:

0.000851

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.000945

Gnomad4 NFE

AF:

0.00224

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00242

Hom.:

Bravo

AF:

0.00137

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00314

AC:

ExAC

AF:

0.00115

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Dec 08, 2023

The c.416C>T (p.P139L) alteration is located in exon 5 (coding exon 5) of the KIAA0922 gene. This alteration results from a C to T substitution at nucleotide position 416, causing the proline (P) at amino acid position 139 to be replaced by a leucine (L). 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

0.15

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

T;.

Eigen

Benign

-0.038

Eigen_PC

Benign

-0.044

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.055

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

2.0

M;M

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.93

N;N

REVEL

Benign

0.18

Sift

Benign

0.048

D;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.97

D;D

Vest4

0.28

MVP

0.043

MPC

0.44

ClinPred

0.29

GERP RS

4.9

Varity_R

0.055

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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