Variant X-100599152-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The ENST00000373031.5(TNMD):c.714A>C(p.Ala238=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,198,065 control chromosomes in the GnomAD database, including 6 homozygotes. There are 726 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., 38 hem., cov: 23)

Exomes 𝑓: 0.0019 ( 6 hom. 688 hem. )

Consequence

TNMD
ENST00000373031.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.342

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 Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant X-100599152-A-C is Benign according to our data. Variant chrX-100599152-A-C is described in ClinVar as [Benign]. Clinvar id is 729593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.342 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 38 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNMD	NM_022144.3 linkuse as main transcript	c.714A>C	p.Ala238=	synonymous_variant	6/7	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.714A>C	p.Ala238=	synonymous_variant	6/7	1	NM_022144.3	ENSP00000362122	P1	Q9H2S6-1

Frequencies

GnomAD3 genomes

AF:

0.00117

AC:

130

AN:

111379

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

33551

show subpopulations

Gnomad AFR

AF:

0.000262

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000573

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.000496

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00200

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00105

AC:

178

AN:

169039

Hom.:

AF XY:

0.00106

AC XY:

AN XY:

54587

show subpopulations

Gnomad AFR exome

AF:

0.000238

Gnomad AMR exome

AF:

0.000480

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00277

Gnomad FIN exome

AF:

0.0000639

Gnomad NFE exome

AF:

0.00152

Gnomad OTH exome

AF:

0.000723

GnomAD4 exome

AF:

0.00189

AC:

2053

AN:

1086630

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

688

AN XY:

353180

show subpopulations

Gnomad4 AFR exome

AF:

0.000230

Gnomad4 AMR exome

AF:

0.000413

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00372

Gnomad4 FIN exome

AF:

0.000347

Gnomad4 NFE exome

AF:

0.00211

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.00117

AC:

130

AN:

111435

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

33617

show subpopulations

Gnomad4 AFR

AF:

0.000261

Gnomad4 AMR

AF:

0.000572

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.000496

Gnomad4 NFE

AF:

0.00200

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00161

Hom.:

Bravo

AF:

0.000990

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.72

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