Variant 4-153550091-T-G 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.258T>G(p.Phe86Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000298 in 1,491,564 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 1 hom. )

Consequence

TMEM131L
NM_001131007.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.363

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.014591068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM131L	NM_001131007.2 link	c.258T>G	p.Phe86Leu	missense_variant	4/35	ENST00000409959.8	NP_001124479.1	A2VDJ0-5B3KU55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM131L	ENST00000409959.8 link	c.258T>G	p.Phe86Leu	missense_variant	4/35	5	NM_001131007.2	ENSP00000386787.3	A2VDJ0-5
TMEM131L	ENST00000409663.7 link	c.258T>G	p.Phe86Leu	missense_variant	4/35	5		ENSP00000386574.3	A2VDJ0-1
TMEM131L	ENST00000445960.5 link	n.214T>G		non_coding_transcript_exon_variant	3/5	4		ENSP00000413054.1	F8WEQ2

Frequencies

GnomAD3 genomes

AF:

0.000453

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

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:

0.000426

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000240

AC:

AN:

133512

Hom.:

AF XY:

0.000170

AC XY:

AN XY:

70688

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000920

Gnomad ASJ exome

AF:

0.000129

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000186

Gnomad OTH exome

AF:

0.00109

GnomAD4 exome

AF:

0.000280

AC:

375

AN:

1339374

Hom.:

Cov.:

AF XY:

0.000280

AC XY:

185

AN XY:

660972

show subpopulations

Gnomad4 AFR exome

AF:

0.000135

Gnomad4 AMR exome

AF:

0.00122

Gnomad4 ASJ exome

AF:

0.0000416

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000296

Gnomad4 OTH exome

AF:

0.000451

GnomAD4 genome

AF:

0.000453

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00236

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.000308

Hom.:

Bravo

AF:

0.000593

ExAC

AF:

0.0000853

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

May 20, 2024

The c.258T>G (p.F86L) alteration is located in exon 4 (coding exon 4) of the KIAA0922 gene. This alteration results from a T to G substitution at nucleotide position 258, causing the phenylalanine (F) at amino acid position 86 to be replaced by a leucine (L). 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

Uncertain

0.48

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.69

CADD

Benign

4.9

DANN

Benign

0.55

DEOGEN2

Benign

0.00086

T;.

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.6

L;L

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.45

N;N

REVEL

Benign

0.048

Sift

Benign

0.63

T;T

Sift4G

Benign

0.96

T;T

Polyphen

0.0010

B;B

Vest4

0.20

MutPred

0.24

Gain of glycosylation at S82 (P = 0.0387);Gain of glycosylation at S82 (P = 0.0387);

MVP

0.043

MPC

0.12

ClinPred

0.014

GERP RS

-1.4

Varity_R

0.032

gMVP

0.25

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