X-100594054-T-C

Position:

• chrX-100594054-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022144.3(TNMD):​c.321+19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 1,194,498 control chromosomes in the GnomAD database, including 58,885 homozygotes. There are 145,269 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 0.40 (6432 hom., 12055 hem., cov: 20)
  • Exomes 𝑓: 0.37 (52453 hom. 133214 hem.)
• Consequence: TNMD NM_022144.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNMD	NM_022144.3	c.321+19T>C		intron_variant		ENST00000373031.5	NP_071427.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNMD	ENST00000373031.5	c.321+19T>C		intron_variant		1	NM_022144.3	ENSP00000362122.4
TNMD	ENST00000485971.1	n.412+19T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.397 AC: 43166 AN: 108788 Hom.: 6429 Cov.: 20 AF XY: 0.386 AC XY: 12038 AN XY: 31164

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.410

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.435

GnomAD3 exomes AF: 0.409 AC: 71495 AN: 174621 Hom.: 10170 AF XY: 0.408 AC XY: 24411 AN XY: 59867

Gnomad AFR exome AF: 0.446

Gnomad AMR exome AF: 0.461

Gnomad ASJ exome AF: 0.399

Gnomad EAS exome AF: 0.684

Gnomad SAS exome AF: 0.380

Gnomad FIN exome AF: 0.344

Gnomad NFE exome AF: 0.360

Gnomad OTH exome AF: 0.412

GnomAD4 exome AF: 0.375 AC: 407050 AN: 1085656 Hom.: 52453 Cov.: 28 AF XY: 0.378 AC XY: 133214 AN XY: 352780

Gnomad4 AFR exome AF: 0.443

Gnomad4 AMR exome AF: 0.464

Gnomad4 ASJ exome AF: 0.393

Gnomad4 EAS exome AF: 0.648

Gnomad4 SAS exome AF: 0.376

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.358

Gnomad4 OTH exome AF: 0.404

GnomAD4 genome AF: 0.397 AC: 43193 AN: 108842 Hom.: 6432 Cov.: 20 AF XY: 0.386 AC XY: 12055 AN XY: 31228

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.441

Alfa AF: 0.387 Hom.: 4725

Bravo AF: 0.417

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.48

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: rs2073163; hg19: chrX-99849051; COSMIC: COSV65977231;