Genetic Variant TNMD:p.Gln197Glu (chrX-100599027-C-G) – 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_022144.3(TNMD):c.589C>G(p.Gln197Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000335 in 1,193,384 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Consequence

TNMD
NM_022144.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.25

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11046687).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022144.3. 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
	TNMD	NM_022144.3	MANE Select	c.589C>G	p.Gln197Glu	missense	Exon 6 of 7	NP_071427.2	Q9H2S6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNMD	ENST00000373031.5	TSL:1 MANE Select	c.589C>G	p.Gln197Glu	missense	Exon 6 of 7	ENSP00000362122.4	Q9H2S6-1
	ENSG00000301679	ENST00000780746.1		n.77+7167G>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

110957

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000658

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000601

AC:

AN:

166516

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000799

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000185

AC:

AN:

1082427

Hom.:

Cov.:

AF XY:

0.00000286

AC XY:

AN XY:

350019

show subpopulations

African (AFR)

AF:

0.0000773

AC:

AN:

25868

American (AMR)

AF:

0.00

AC:

AN:

33499

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18789

East Asian (EAS)

AF:

0.00

AC:

AN:

29869

South Asian (SAS)

AF:

0.00

AC:

AN:

50303

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40228

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4059

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

834429

Other (OTH)

AF:

0.00

AC:

AN:

45383

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

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:

0.0000180

AC:

AN:

110957

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33207

show subpopulations

African (AFR)

AF:

0.0000658

AC:

AN:

30390

American (AMR)

AF:

0.00

AC:

AN:

10413

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2634

East Asian (EAS)

AF:

0.00

AC:

AN:

3549

South Asian (SAS)

AF:

0.00

AC:

AN:

2591

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5908

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53052

Other (OTH)

AF:

0.00

AC:

AN:

1497

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

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

0.065

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.20

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.67

M_CAP

Benign

0.0042

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

2.3

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.19

REVEL

Benign

0.035

Sift

Benign

0.079

Sift4G

Benign

0.75

Polyphen

0.010

Vest4

0.18

MutPred

0.21

Gain of disorder (P = 0.0606)

MVP

0.19

MPC

0.34

ClinPred

0.092

GERP RS

5.8

Varity_R

0.12

gMVP

0.45

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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