Variant 4-153466405-G-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.8G>T(p.Gly3Val) variant causes a missense change. The variant allele was found at a frequency of 0.000164 in 1,343,502 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

TMEM131L
NM_001131007.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.26

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=0.08407706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM131L	NM_001131007.2 linkuse as main transcript	c.8G>T	p.Gly3Val	missense_variant	1/35	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.8G>T	p.Gly3Val	missense_variant	1/35	5	NM_001131007.2	ENSP00000386787	A2	A2VDJ0-5
TMEM131L	ENST00000409663.7 linkuse as main transcript	c.8G>T	p.Gly3Val	missense_variant	1/35	5		ENSP00000386574	P4	A2VDJ0-1
TMEM131L	ENST00000445960.5 linkuse as main transcript	c.8G>T	p.Gly3Val	missense_variant, NMD_transcript_variant	1/5	4		ENSP00000413054

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

151318

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000962

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000237

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000189

AC:

AN:

47718

Hom.:

AF XY:

0.000286

AC XY:

AN XY:

28014

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000119

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:

0.000329

Gnomad OTH exome

AF:

0.00145

GnomAD4 exome

AF:

0.000170

AC:

203

AN:

1192184

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

100

AN XY:

581896

show subpopulations

Gnomad4 AFR exome

AF:

0.0000402

Gnomad4 AMR exome

AF:

0.000274

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000185

Gnomad4 NFE exome

AF:

0.000191

Gnomad4 OTH exome

AF:

0.000125

GnomAD4 genome

AF:

0.000112

AC:

AN:

151318

Hom.:

Cov.:

AF XY:

0.0000541

AC XY:

AN XY:

73886

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000962

Gnomad4 NFE

AF:

0.000237

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000147

ExAC

AF:

0.0000652

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

Jul 20, 2021

The c.8G>T (p.G3V) alteration is located in exon 1 (coding exon 1) of the KIAA0922 gene. This alteration results from a G to T substitution at nucleotide position 8, causing the glycine (G) at amino acid position 3 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

0.31

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0039

T;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.80

T;T

M_CAP

Pathogenic

0.67

MetaRNN

Benign

0.084

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.093

Sift

Uncertain

0.0060

D;D

Sift4G

Benign

0.075

T;T

Polyphen

0.98

D;D

Vest4

0.31

MVP

0.043

MPC

0.57

ClinPred

0.11

GERP RS

3.3

Varity_R

0.28

gMVP

0.49

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