Genetic Variant TNMD:p.Val115Leu (chrX-100594282-G-C) – 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_022144.3(TNMD):c.343G>C(p.Val115Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000921 in 1,085,578 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V115M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 21)

Exomes 𝑓: 9.2e-7 ( 0 hom. 0 hem. )

Consequence

TNMD
NM_022144.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.69

Publications

0 publications found

Variant links:

Genes affected

TNMD (HGNC:17757): (tenomodulin) This gene encodes a protein that is related to chondromodulin-I, which is a cartilage-specific glycoprotein that functions to stimulate chondrocyte growth and to inhibit tube formation of endothelial cells. This protein is also an angiogenesis inhibitor. Genetic variation in this gene is associated with a risk for type 2 diabetes, central obesity and serum levels of systemic immune mediators in a body size-dependent manner. This gene is also a candidate gene for age-related macular degeneration, though a direct link has yet to be demonstrated. [provided by RefSeq, Sep 2009]

TNMD links:

ENSG00000301679 (HGNC:):

ENSG00000301679 links:

Genome browser will be placed here

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=0.41236445).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNMD	NM_022144.3 link	c.343G>C	p.Val115Leu	missense_variant	Exon 4 of 7	ENST00000373031.5	NP_071427.2	Q9H2S6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNMD	ENST00000373031.5 link	c.343G>C	p.Val115Leu	missense_variant	Exon 4 of 7	1	NM_022144.3	ENSP00000362122.4	Q9H2S6-1
TNMD	ENST00000485971.1 link	n.434G>C		non_coding_transcript_exon_variant	Exon 2 of 3	3
ENSG00000301679	ENST00000780746.1 link	n.77+11912C>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.21e-7

AC:

AN:

1085578

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

352174

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26186

American (AMR)

AF:

0.00

AC:

AN:

34629

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19103

East Asian (EAS)

AF:

0.00

AC:

AN:

30006

South Asian (SAS)

AF:

0.00

AC:

AN:

51657

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40266

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4087

European-Non Finnish (NFE)

AF:

0.00000120

AC:

AN:

833997

Other (OTH)

AF:

0.00

AC:

AN:

45647

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

M_CAP

Pathogenic

0.55

MetaRNN

Benign

0.41

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

0.76

PhyloP100

4.7

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.91

REVEL

Uncertain

0.33

Sift

Benign

0.041

Sift4G

Benign

0.072

Polyphen

0.62

Vest4

0.32

MutPred

0.53

Loss of catalytic residue at V115 (P = 0.1459);

MVP

0.67

MPC

0.30

ClinPred

0.63

GERP RS

5.9

Varity_R

0.32

gMVP

0.83

Mutation Taster

=81/19

polymorphism

(source)

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

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over