Genetic Variant NM_001131007.2:c.113C>T (chr4-153466510-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001131007.2(TMEM131L):c.113C>T(p.Ala38Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,397,648 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 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

TMEM131L
NM_001131007.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1986393).

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.113C>T	p.Ala38Val	missense	Exon 1 of 35	NP_001124479.1	A2VDJ0-5
	TMEM131L	NM_015196.4		c.113C>T	p.Ala38Val	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.113C>T	p.Ala38Val	missense	Exon 1 of 35	ENSP00000386787.3	A2VDJ0-5
TMEM131L	ENST00000409663.7	TSL:5	c.113C>T	p.Ala38Val	missense	Exon 1 of 35	ENSP00000386574.3	A2VDJ0-1
TMEM131L	ENST00000886543.1		c.113C>T	p.Ala38Val	missense	Exon 1 of 35	ENSP00000556606.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152010

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:

0.00000161

AC:

AN:

1245638

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

612344

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26234

American (AMR)

AF:

0.00

AC:

AN:

25794

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21244

East Asian (EAS)

AF:

0.00

AC:

AN:

28204

South Asian (SAS)

AF:

0.00

AC:

AN:

59202

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31202

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4910

European-Non Finnish (NFE)

AF:

0.00000200

AC:

AN:

998464

Other (OTH)

AF:

0.00

AC:

AN:

50384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00000658

AC:

AN:

152010

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41424

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67972

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000151

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

Uncertain

0.38

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0030

Eigen

Benign

0.045

Eigen_PC

Benign

-0.050

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.83

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

PhyloP100

1.3

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.94

REVEL

Benign

0.11

Sift

Benign

0.034

Sift4G

Uncertain

0.022

Polyphen

1.0

Vest4

0.12

MutPred

0.28

Loss of glycosylation at P35 (P = 0.0659)

MVP

0.043

MPC

0.29

ClinPred

0.80

GERP RS

2.6

PromoterAI

0.014

Neutral

(source)

Varity_R

0.11

gMVP

0.44

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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