Variant 4-153586227-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001131007.2(TMEM131L):c.1330C>T(p.Pro444Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000446 in 1,570,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

TMEM131L
NM_001131007.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.34

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.803

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM131L	NM_001131007.2 linkuse as main transcript	c.1330C>T	p.Pro444Ser	missense_variant	14/35	ENST00000409959.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM131L	ENST00000409959.8 linkuse as main transcript	c.1330C>T	p.Pro444Ser	missense_variant	14/35	5	NM_001131007.2	A2	A2VDJ0-5
TMEM131L	ENST00000240487.5 linkuse as main transcript	c.913C>T	p.Pro305Ser	missense_variant	10/29	1
TMEM131L	ENST00000409663.7 linkuse as main transcript	c.1327C>T	p.Pro443Ser	missense_variant	14/35	5		P4	A2VDJ0-1
TMEM131L	ENST00000509565.1 linkuse as main transcript	n.405C>T		non_coding_transcript_exon_variant	4/4	4

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151986

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000423

AC:

AN:

1418116

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

703514

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:

0.00000365

Gnomad4 OTH exome

AF:

0.0000341

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151986

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74226

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:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

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 08, 2024

The c.1330C>T (p.P444S) alteration is located in exon 14 (coding exon 14) of the KIAA0922 gene. This alteration results from a C to T substitution at nucleotide position 1330, causing the proline (P) at amino acid position 444 to be replaced by a serine (S). 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

0.26

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

Cadd

Uncertain

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.12

T;.;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.033

MetaRNN

Pathogenic

0.80

D;D;D

MetaSVM

Uncertain

-0.20

MutationAssessor

Uncertain

2.5

M;.;.

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-4.3

D;D;D

REVEL

Uncertain

0.57

Sift

Benign

0.099

T;T;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.77

P;P;.

Vest4

0.63

MutPred

0.72

Loss of glycosylation at P448 (P = 0.08);.;.;

MVP

0.42

MPC

0.49

ClinPred

0.99

GERP RS

5.7

Varity_R

0.19

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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