rs4828037

Variant names:

• chrX-100590687-T-C
• rs4828037
• NM_022144.3:c.181-3208T>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.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
• Publications: 9 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=-0.86).
• 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 rank	MANE	Protein	UniProt
TNMD	NM_022144.3	c.181-3208T>C		intron_variant	Intron 2 of 6	ENST00000373031.5	NP_071427.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNMD	ENST00000373031.5	c.181-3208T>C		intron_variant	Intron 2 of 6	1	NM_022144.3	ENSP00000362122.4
ENSG00000301679	ENST00000780746.1	n.77+15507A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 45252 AN: 110402 Hom.: 7032 Cov.: 22

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

African (AFR) AF: 0.525 AC: 15904 AN: 30303

American (AMR) AF: 0.361 AC: 3774 AN: 10443

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1154 AN: 2639

East Asian (EAS) AF: 0.142 AC: 497 AN: 3512

South Asian (SAS) AF: 0.478 AC: 1219 AN: 2552

European-Finnish (FIN) AF: 0.352 AC: 2064 AN: 5858

Middle Eastern (MID) AF: 0.327 AC: 70 AN: 214

European-Non Finnish (NFE) AF: 0.374 AC: 19721 AN: 52749

Other (OTH) AF: 0.378 AC: 571 AN: 1509

Alfa AF: 0.388 Hom.: 20243

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
PhyloP100		-0.81
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: rs4828037; hg19: chrX-99845684;