rs2073162

Variant names:

• chrX-100594020-G-A
• rs2073162
• NM_022144.3:c.306G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 18 publications found

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]

ENSG00000301679 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• 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	c.306G>A	p.Val102Val	synonymous_variant	Exon 3 of 7	ENST00000373031.5	NP_071427.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNMD	ENST00000373031.5	c.306G>A	p.Val102Val	synonymous_variant	Exon 3 of 7	1	NM_022144.3	ENSP00000362122.4
TNMD	ENST00000485971.1	n.397G>A		non_coding_transcript_exon_variant	Exon 1 of 3	3
ENSG00000301679	ENST00000780746.1	n.77+12174C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.395 AC: 43282 AN: 109685 Hom.: 6299 Cov.: 21

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

GnomAD2 exomes AF: 0.403 AC: 72959 AN: 181153 AF XY: 0.395

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 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

African (AFR) AF: 0.432 AC: 11382 AN: 26356

American (AMR) AF: 0.456 AC: 16006 AN: 35072

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 7499 AN: 19331

East Asian (EAS) AF: 0.642 AC: 19353 AN: 30158

South Asian (SAS) AF: 0.363 AC: 19544 AN: 53805

European-Finnish (FIN) AF: 0.347 AC: 14023 AN: 40470

Middle Eastern (MID) AF: 0.422 AC: 1742 AN: 4126

European-Non Finnish (NFE) AF: 0.355 AC: 298145 AN: 840690

Other (OTH) AF: 0.399 AC: 18378 AN: 46020

GnomAD4 genome AF: 0.395 AC: 43306 AN: 109738 Hom.: 6301 Cov.: 21 AF XY: 0.388 AC XY: 12465 AN XY: 32090

African (AFR) AF: 0.430 AC: 13001 AN: 30205

American (AMR) AF: 0.459 AC: 4742 AN: 10336

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1018 AN: 2608

East Asian (EAS) AF: 0.667 AC: 2272 AN: 3405

South Asian (SAS) AF: 0.367 AC: 919 AN: 2507

European-Finnish (FIN) AF: 0.336 AC: 1924 AN: 5734

Middle Eastern (MID) AF: 0.416 AC: 89 AN: 214

European-Non Finnish (NFE) AF: 0.351 AC: 18432 AN: 52554

Other (OTH) AF: 0.437 AC: 657 AN: 1502

Alfa AF: 0.376 Hom.: 46338

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
PhyloP100		0.0010
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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