Variant 4-153585582-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001131007.2(TMEM131L):c.1282C>T(p.Leu428Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,613,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

TMEM131L
NM_001131007.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.454

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09235954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM131L	NM_001131007.2 linkuse as main transcript	c.1282C>T	p.Leu428Phe	missense_variant	13/35	ENST00000409959.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM131L	ENST00000409959.8 linkuse as main transcript	c.1282C>T	p.Leu428Phe	missense_variant	13/35	5	NM_001131007.2	A2	A2VDJ0-5
TMEM131L	ENST00000240487.5 linkuse as main transcript	c.865C>T	p.Leu289Phe	missense_variant	9/29	1
TMEM131L	ENST00000409663.7 linkuse as main transcript	c.1279C>T	p.Leu427Phe	missense_variant	13/35	5		P4	A2VDJ0-1
TMEM131L	ENST00000509565.1 linkuse as main transcript	n.357C>T		non_coding_transcript_exon_variant	3/4	4

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000597

AC:

AN:

251116

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000146

AC:

214

AN:

1461424

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.000180

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000152

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.0000547

EpiControl

AF:

0.000119

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

Jun 30, 2022

The c.1282C>T (p.L428F) alteration is located in exon 13 (coding exon 13) of the KIAA0922 gene. This alteration results from a C to T substitution at nucleotide position 1282, causing the leucine (L) at amino acid position 428 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

0.17

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.39

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.024

T;.;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.84

T;T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.092

T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.0

N;.;.

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.3

N;N;N

REVEL

Benign

0.071

Sift

Benign

0.039

D;D;T

Sift4G

Uncertain

0.010

D;D;D

Polyphen

0.015

B;B;.

Vest4

0.16

MutPred

0.44

Gain of catalytic residue at L427 (P = 0.0161);.;.;

MVP

0.082

MPC

0.11

ClinPred

0.066

GERP RS

3.1

Varity_R

0.074

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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