dbSNP rs2073162: TNMD:p.Val102Val (chrX-100594020-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_022144.3(TNMD):c.306G>A(p.Val102Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,205,766 control chromosomes in the GnomAD database, including 57,933 homozygotes. There are 146,401 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.39 ( 6301 hom., 12465 hem., cov: 21)

Exomes 𝑓: 0.37 ( 51632 hom. 133936 hem. )

Consequence

TNMD
NM_022144.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00100

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant X-100594020-G-A is Benign according to our data. Variant chrX-100594020-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.001 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNMD	NM_022144.3 link	c.306G>A	p.Val102Val	synonymous_variant	Exon 3 of 7	ENST00000373031.5	NP_071427.2	Q9H2S6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNMD	ENST00000373031.5 link	c.306G>A	p.Val102Val	synonymous_variant	Exon 3 of 7	1	NM_022144.3	ENSP00000362122.4		Q9H2S6-1
TNMD	ENST00000485971.1 link	n.397G>A		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.395

AC:

43282

AN:

109685

Hom.:

6299

Cov.:

AF XY:

0.389

AC XY:

12450

AN XY:

32027

show subpopulations

Gnomad AFR

AF:

0.431

Gnomad AMI

AF:

0.374

Gnomad AMR

AF:

0.459

Gnomad ASJ

AF:

0.390

Gnomad EAS

AF:

0.667

Gnomad SAS

AF:

0.368

Gnomad FIN

AF:

0.336

Gnomad MID

AF:

0.406

Gnomad NFE

AF:

0.351

Gnomad OTH

AF:

0.432

GnomAD3 exomes

AF:

0.403

AC:

72959

AN:

181153

Hom.:

10075

AF XY:

0.395

AC XY:

25997

AN XY:

65779

show subpopulations

Gnomad AFR exome

AF:

0.437

Gnomad AMR exome

AF:

0.456

Gnomad ASJ exome

AF:

0.390

Gnomad EAS exome

AF:

0.676

Gnomad SAS exome

AF:

0.365

Gnomad FIN exome

AF:

0.344

Gnomad NFE exome

AF:

0.355

Gnomad OTH exome

AF:

0.403

GnomAD4 exome

AF:

0.370

AC:

406072

AN:

1096028

Hom.:

51632

Cov.:

AF XY:

0.370

AC XY:

133936

AN XY:

361930

show subpopulations

Gnomad4 AFR exome

AF:

0.432

Gnomad4 AMR exome

AF:

0.456

Gnomad4 ASJ exome

AF:

0.388

Gnomad4 EAS exome

AF:

0.642

Gnomad4 SAS exome

AF:

0.363

Gnomad4 FIN exome

AF:

0.347

Gnomad4 NFE exome

AF:

0.355

Gnomad4 OTH exome

AF:

0.399

GnomAD4 genome

AF:

0.395

AC:

43306

AN:

109738

Hom.:

6301

Cov.:

AF XY:

0.388

AC XY:

12465

AN XY:

32090

show subpopulations

Gnomad4 AFR

AF:

0.430

Gnomad4 AMR

AF:

0.459

Gnomad4 ASJ

AF:

0.390

Gnomad4 EAS

AF:

0.667

Gnomad4 SAS

AF:

0.367

Gnomad4 FIN

AF:

0.336

Gnomad4 NFE

AF:

0.351

Gnomad4 OTH

AF:

0.437

Alfa

AF:

0.369

Hom.:

34319

Bravo

AF:

0.413

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

3.3

DANN

Benign

0.75

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over