rs2073162

chrX-100594020-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_022144.3(TNMD):c.306G>A(p.Val102=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100

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]

ACMG classification

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/exons	MANE	UniProt
TNMD	NM_022144.3	c.306G>A	p.Val102=	synonymous_variant	3/7	ENST00000373031.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNMD	ENST00000373031.5	c.306G>A	p.Val102=	synonymous_variant	3/7	1	NM_022144.3	P1
TNMD	ENST00000485971.1	n.397G>A		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes AF: 0.395 AC: 43282 AN: 109685 Hom.: 6299 Cov.: 21 AF XY: 0.389 AC XY: 12450 AN XY: 32027

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

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.: 30 AF XY: 0.370 AC XY: 133936 AN XY: 361930

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.: 21 AF XY: 0.388 AC XY: 12465 AN XY: 32090

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

Other links and lift over

dbSNP: rs2073162; hg19: chrX-99849017; COSMIC: COSV65977273;