Variant 4-153558286-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.578C>T(p.Ser193Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,454,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TMEM131L
NM_001131007.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.52

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=0.14214912).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM131L	NM_001131007.2 linkuse as main transcript	c.578C>T	p.Ser193Phe	missense_variant	7/35	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.578C>T	p.Ser193Phe	missense_variant	7/35	5	NM_001131007.2	ENSP00000386787	A2	A2VDJ0-5
TMEM131L	ENST00000240487.5 linkuse as main transcript	c.161C>T	p.Ser54Phe	missense_variant	3/29	1		ENSP00000240487
TMEM131L	ENST00000409663.7 linkuse as main transcript	c.578C>T	p.Ser193Phe	missense_variant	7/35	5		ENSP00000386574	P4	A2VDJ0-1
TMEM131L	ENST00000462540.1 linkuse as main transcript	n.321C>T		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1454978

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723900

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

Cov.:

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

Mar 01, 2023

The c.578C>T (p.S193F) alteration is located in exon 7 (coding exon 7) of the KIAA0922 gene. This alteration results from a C to T substitution at nucleotide position 578, causing the serine (S) at amino acid position 193 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

0.16

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.087

T;.;T

Eigen

Benign

0.10

Eigen_PC

Benign

0.062

FATHMM_MKL

Benign

0.24

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.6

D;D;N

REVEL

Benign

0.16

Sift

Benign

0.042

D;D;D

Sift4G

Uncertain

0.011

D;D;D

Polyphen

0.98

D;D;.

Vest4

0.28

MutPred

0.39

Loss of disorder (P = 0.0098);Loss of disorder (P = 0.0098);.;

MVP

0.043

MPC

0.42

ClinPred

0.98

GERP RS

5.1

Varity_R

0.094

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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