Variant X-100585042-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000373031.5(TNMD):c.24T>C(p.Asn8=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,208,785 control chromosomes in the GnomAD database, including 53 homozygotes. There are 815 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 32 hom., 410 hem., cov: 22)

Exomes 𝑓: 0.0014 ( 21 hom. 405 hem. )

Consequence

TNMD
ENST00000373031.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.89

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant X-100585042-T-C is Benign according to our data. Variant chrX-100585042-T-C is described in ClinVar as [Benign]. Clinvar id is 780711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.89 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0135 (1512/111964) while in subpopulation AFR AF= 0.047 (1448/30798). AF 95% confidence interval is 0.045. There are 32 homozygotes in gnomad4. There are 410 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 32 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNMD	NM_022144.3 linkuse as main transcript	c.24T>C	p.Asn8=	synonymous_variant	1/7	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.24T>C	p.Asn8=	synonymous_variant	1/7	1	NM_022144.3	ENSP00000362122	P1	Q9H2S6-1

Frequencies

GnomAD3 genomes

AF:

0.0135

AC:

1513

AN:

111909

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

407

AN XY:

34075

show subpopulations

Gnomad AFR

AF:

0.0472

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00446

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:

0.000113

Gnomad OTH

AF:

0.00730

GnomAD3 exomes

AF:

0.00402

AC:

730

AN:

181497

Hom.:

AF XY:

0.00268

AC XY:

177

AN XY:

66129

show subpopulations

Gnomad AFR exome

AF:

0.0495

Gnomad AMR exome

AF:

0.00254

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000617

Gnomad OTH exome

AF:

0.00156

GnomAD4 exome

AF:

0.00137

AC:

1500

AN:

1096821

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

405

AN XY:

362401

show subpopulations

Gnomad4 AFR exome

AF:

0.0473

Gnomad4 AMR exome

AF:

0.00296

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000416

Gnomad4 OTH exome

AF:

0.00230

GnomAD4 genome

AF:

0.0135

AC:

1512

AN:

111964

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

410

AN XY:

34140

show subpopulations

Gnomad4 AFR

AF:

0.0470

Gnomad4 AMR

AF:

0.00445

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000113

Gnomad4 OTH

AF:

0.00721

Alfa

AF:

0.00445

Hom.:

Bravo

AF:

0.0158

EpiCase

AF:

0.00

EpiControl

AF:

0.000417

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	Jul 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

8.5

DANN

Benign

0.55

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