Genetic Variant TMEM131L:p.Pro7Ser (chr4-153466416-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001131007.2(TMEM131L):c.19C>T(p.Pro7Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000019 in 1,368,060 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: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

TMEM131L
NM_001131007.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.06

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30985284).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001131007.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM131L	NM_001131007.2	MANE Select	c.19C>T	p.Pro7Ser	missense	Exon 1 of 35	NP_001124479.1	A2VDJ0-5
	TMEM131L	NM_015196.4		c.19C>T	p.Pro7Ser	missense	Exon 1 of 35	NP_056011.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM131L	ENST00000409959.8	TSL:5 MANE Select	c.19C>T	p.Pro7Ser	missense	Exon 1 of 35	ENSP00000386787.3	A2VDJ0-5
TMEM131L	ENST00000409663.7	TSL:5	c.19C>T	p.Pro7Ser	missense	Exon 1 of 35	ENSP00000386574.3	A2VDJ0-1
TMEM131L	ENST00000886543.1		c.19C>T	p.Pro7Ser	missense	Exon 1 of 35	ENSP00000556606.1

Frequencies

GnomAD3 genomes

AF:

0.0000463

AC:

AN:

151350

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:

0.000104

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000160

AC:

AN:

62590

AF XY:

0.0000280

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000426

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000156

AC:

AN:

1216710

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

595466

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25574

American (AMR)

AF:

0.00

AC:

AN:

22140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20014

East Asian (EAS)

AF:

0.00

AC:

AN:

27492

South Asian (SAS)

AF:

0.00

AC:

AN:

54924

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28366

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3410

European-Non Finnish (NFE)

AF:

0.0000183

AC:

AN:

985724

Other (OTH)

AF:

0.0000204

AC:

AN:

49066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000463

AC:

AN:

151350

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73866

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41378

American (AMR)

AF:

0.00

AC:

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3444

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.000104

AC:

AN:

67580

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.539

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0015

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.78

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.31

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PhyloP100

4.1

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.50

REVEL

Benign

0.080

Sift

Pathogenic

0.0

Sift4G

Benign

0.34

Polyphen

1.0

Vest4

0.35

MVP

0.043

MPC

0.52

ClinPred

0.42

GERP RS

2.4

PromoterAI

0.026

Neutral

(source)

Varity_R

0.15

gMVP

0.28

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over