X-100594054-T-C

Variant names:

• chrX-100594054-T-C
• rs2073163
• NM_022144.3:c.321+19T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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 -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 rank	MANE	Protein	UniProt
TNMD	NM_022144.3	c.321+19T>C		intron_variant	Intron 3 of 6	ENST00000373031.5	NP_071427.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNMD	ENST00000373031.5	c.321+19T>C		intron_variant	Intron 3 of 6	1	NM_022144.3	ENSP00000362122.4
TNMD	ENST00000485971.1	n.412+19T>C		intron_variant	Intron 1 of 2	3
ENSG00000301679	ENST00000780746.1	n.77+12140A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 43166 AN: 108788 Hom.: 6429 Cov.: 20

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

GnomAD2 exomes AF: 0.409 AC: 71495 AN: 174621 AF XY: 0.408

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 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

African (AFR) AF: 0.443 AC: 11559 AN: 26116

American (AMR) AF: 0.464 AC: 15947 AN: 34398

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 7474 AN: 19021

East Asian (EAS) AF: 0.648 AC: 19462 AN: 30039

South Asian (SAS) AF: 0.376 AC: 19565 AN: 51974

European-Finnish (FIN) AF: 0.348 AC: 14010 AN: 40250

Middle Eastern (MID) AF: 0.428 AC: 1736 AN: 4055

European-Non Finnish (NFE) AF: 0.358 AC: 298888 AN: 834214

Other (OTH) AF: 0.404 AC: 18409 AN: 45589

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

African (AFR) AF: 0.436 AC: 13034 AN: 29884

American (AMR) AF: 0.462 AC: 4726 AN: 10239

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1017 AN: 2608

East Asian (EAS) AF: 0.669 AC: 2254 AN: 3369

South Asian (SAS) AF: 0.370 AC: 896 AN: 2422

European-Finnish (FIN) AF: 0.331 AC: 1869 AN: 5643

Middle Eastern (MID) AF: 0.421 AC: 90 AN: 214

European-Non Finnish (NFE) AF: 0.352 AC: 18406 AN: 52314

Other (OTH) AF: 0.441 AC: 653 AN: 1482

Alfa AF: 0.391 Hom.: 8151

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
PhyloP100		-0.23
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: rs2073163; hg19: chrX-99849051; COSMIC: COSV65977231;