rs4828037

chrX-100590687-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.181-3208T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 110,451 control chromosomes in the GnomAD database, including 7,032 homozygotes. There are 13,005 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 0.41 (7032 hom., 13005 hem., cov: 22)
• Consequence: TNMD NM_022144.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.808

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNMD	NM_022144.3	c.181-3208T>C		intron_variant		ENST00000373031.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNMD	ENST00000373031.5	c.181-3208T>C		intron_variant		1	NM_022144.3	P1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 45252 AN: 110402 Hom.: 7032 Cov.: 22 AF XY: 0.398 AC XY: 12987 AN XY: 32664

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.378

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.410 AC: 45263 AN: 110451 Hom.: 7032 Cov.: 22 AF XY: 0.397 AC XY: 13005 AN XY: 32723

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.378

Alfa AF: 0.389 Hom.: 9936

Bravo AF: 0.413

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.28
Dann	Benign	0.77

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: rs4828037; hg19: chrX-99845684;