Variant 4-153584835-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001131007.2(TMEM131L):c.1061C>T(p.Ala354Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,610,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

TMEM131L
NM_001131007.2 missense, splice_region

Scores

Splicing: ADA: 0.1999

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.062284976).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM131L	NM_001131007.2 linkuse as main transcript	c.1061C>T	p.Ala354Val	missense_variant, splice_region_variant	12/35	ENST00000409959.8	NP_001124479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM131L	ENST00000409959.8 linkuse as main transcript	c.1061C>T	p.Ala354Val	missense_variant, splice_region_variant	12/35	5	NM_001131007.2	ENSP00000386787	A2	A2VDJ0-5
TMEM131L	ENST00000240487.5 linkuse as main transcript	c.644C>T	p.Ala215Val	missense_variant, splice_region_variant	8/29	1		ENSP00000240487
TMEM131L	ENST00000409663.7 linkuse as main transcript	c.1061-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000386574	P4	A2VDJ0-1
TMEM131L	ENST00000509565.1 linkuse as main transcript	n.136C>T		splice_region_variant, non_coding_transcript_exon_variant	2/4	4

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.000206

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000143

AC:

AN:

251240

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

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:

0.000299

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000305

AC:

445

AN:

1458578

Hom.:

Cov.:

AF XY:

0.000287

AC XY:

208

AN XY:

725836

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.0000224

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:

0.000371

Gnomad4 OTH exome

AF:

0.000498

GnomAD4 genome

AF:

0.000145

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000262

Hom.:

Bravo

AF:

0.000144

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000157

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

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

Nov 29, 2023

The c.1061C>T (p.A354V) alteration is located in exon 12 (coding exon 12) of the KIAA0922 gene. This alteration results from a C to T substitution at nucleotide position 1061, causing the alanine (A) at amino acid position 354 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

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.043

.;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.062

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.63

D;D;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.018

Sift

Uncertain

0.0050

D;D

Sift4G

Benign

0.066

T;T

Polyphen

0.026

B;.

Vest4

0.28

MVP

0.068

MPC

0.20

ClinPred

0.094

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.20

dbscSNV1_RF

Benign

0.23

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