Variant 4-153467211-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001131007.2(TMEM131L):c.125C>T(p.Ala42Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00293 in 1,551,634 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 13 hom. )

Consequence

TMEM131L
NM_001131007.2 missense, splice_region

Scores

Splicing: ADA: 0.9797

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.42

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005273938).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM131L	NM_001131007.2 linkuse as main transcript	c.125C>T	p.Ala42Val	missense_variant, splice_region_variant	2/35	ENST00000409959.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM131L	ENST00000409959.8 linkuse as main transcript	c.125C>T	p.Ala42Val	missense_variant, splice_region_variant	2/35	5	NM_001131007.2	A2	A2VDJ0-5
TMEM131L	ENST00000409663.7 linkuse as main transcript	c.125C>T	p.Ala42Val	missense_variant, splice_region_variant	2/35	5		P4	A2VDJ0-1
TMEM131L	ENST00000445960.5 linkuse as main transcript	c.125C>T	p.Ala42Val	missense_variant, splice_region_variant, NMD_transcript_variant	2/5	4

Frequencies

GnomAD3 genomes

AF:

0.00183

AC:

278

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00331

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00146

AC:

225

AN:

154118

Hom.:

AF XY:

0.00149

AC XY:

122

AN XY:

81774

show subpopulations

Gnomad AFR exome

AF:

0.00114

Gnomad AMR exome

AF:

0.000122

Gnomad ASJ exome

AF:

0.000942

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000439

Gnomad FIN exome

AF:

0.000588

Gnomad NFE exome

AF:

0.00318

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00305

AC:

4274

AN:

1399346

Hom.:

Cov.:

AF XY:

0.00297

AC XY:

2052

AN XY:

690190

show subpopulations

Gnomad4 AFR exome

AF:

0.000633

Gnomad4 AMR exome

AF:

0.000140

Gnomad4 ASJ exome

AF:

0.000556

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000252

Gnomad4 FIN exome

AF:

0.00148

Gnomad4 NFE exome

AF:

0.00373

Gnomad4 OTH exome

AF:

0.00243

GnomAD4 genome

AF:

0.00183

AC:

278

AN:

152288

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

123

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00331

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00282

Hom.:

Bravo

AF:

0.00165

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00471

AC:

ExAC

AF:

0.00148

AC:

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

Feb 10, 2023

The c.125C>T (p.A42V) alteration is located in exon 2 (coding exon 2) of the KIAA0922 gene. This alteration results from a C to T substitution at nucleotide position 125, causing the alanine (A) at amino acid position 42 to be replaced by a valine (V). 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

0.14

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.0043

T;.

Eigen

Benign

0.080

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.053

MetaRNN

Benign

0.0053

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

L;L

MutationTaster

Benign

0.99

D;D;N

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.035

Sift

Benign

0.20

T;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.26

B;B

Vest4

0.17

MVP

0.043

MPC

0.12

ClinPred

0.80

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.98

dbscSNV1_RF

Benign

0.72

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