Variant X-100599665-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000373031.5(TNMD):c.902G>A(p.Arg301His) variant causes a missense change. The variant allele was found at a frequency of 0.000114 in 1,209,873 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 50 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000081 ( 0 hom., 4 hem., cov: 22)

Exomes 𝑓: 0.00012 ( 0 hom. 46 hem. )

Consequence

TNMD
ENST00000373031.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.32

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18937889).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNMD	NM_022144.3 linkuse as main transcript	c.902G>A	p.Arg301His	missense_variant	7/7	ENST00000373031.5	NP_071427.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNMD	ENST00000373031.5 linkuse as main transcript	c.902G>A	p.Arg301His	missense_variant	7/7	1	NM_022144.3	ENSP00000362122	P1	Q9H2S6-1

Frequencies

GnomAD3 genomes

AF:

0.0000805

AC:

AN:

111748

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33938

show subpopulations

Gnomad AFR

AF:

0.000130

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:

0.0000940

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000547

AC:

AN:

182777

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

67247

show subpopulations

Gnomad AFR exome

AF:

0.0000762

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000529

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000857

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.000117

AC:

129

AN:

1098074

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

363432

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000370

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000148

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000805

AC:

AN:

111799

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33999

show subpopulations

Gnomad4 AFR

AF:

0.000130

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000940

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.0000577

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

Jan 04, 2022

The c.902G>A (p.R301H) alteration is located in exon 7 (coding exon 7) of the TNMD gene. This alteration results from a G to A substitution at nucleotide position 902, causing the arginine (R) at amino acid position 301 to be replaced by a histidine (H). 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

Pathogenic

0.59

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.43

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.72

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.92

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.15

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.052

Polyphen

0.10

Vest4

0.17

MVP

0.22

MPC

1.1

ClinPred

0.20

GERP RS

5.0

Varity_R

0.65

gMVP

0.94

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