X-100589509-G-T

Variant names:

• chrX-100589509-G-T
• rs5966709
• NM_022144.3:c.180+4147G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022144.3(TNMD):​c.180+4147G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 110,195 control chromosomes in the GnomAD database, including 6,692 homozygotes. There are 12,542 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 (6692 hom., 12542 hem., cov: 22)
• Consequence: TNMD NM_022144.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256
• Publications: 14 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNMD	NM_022144.3	c.180+4147G>T		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.180+4147G>T		intron_variant	Intron 2 of 6	1	NM_022144.3	ENSP00000362122.4
ENSG00000301679	ENST00000780746.1	n.77+16685C>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 43929 AN: 110142 Hom.: 6692 Cov.: 22

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.311

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.399 AC: 43942 AN: 110195 Hom.: 6692 Cov.: 22 AF XY: 0.386 AC XY: 12542 AN XY: 32517

African (AFR) AF: 0.513 AC: 15528 AN: 30249

American (AMR) AF: 0.349 AC: 3612 AN: 10348

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1132 AN: 2623

East Asian (EAS) AF: 0.127 AC: 447 AN: 3513

South Asian (SAS) AF: 0.470 AC: 1201 AN: 2558

European-Finnish (FIN) AF: 0.332 AC: 1920 AN: 5784

Middle Eastern (MID) AF: 0.305 AC: 65 AN: 213

European-Non Finnish (NFE) AF: 0.364 AC: 19193 AN: 52725

Other (OTH) AF: 0.368 AC: 557 AN: 1514

Alfa AF: 0.377 Hom.: 45386

Bravo AF: 0.402

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.59
PhyloP100		0.26
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: rs5966709; hg19: chrX-99844506;