X-100598284-C-T

Variant names:

• chrX-100598284-C-T
• rs1155974
• NM_022144.3:c.577+627C>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.577+627C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 110,000 control chromosomes in the GnomAD database, including 4,919 homozygotes. There are 10,953 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 0.35 (4919 hom., 10953 hem., cov: 22)
• Consequence: TNMD NM_022144.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022144.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNMD	NM_022144.3	MANE Select	c.577+627C>T		intron	N/A	NP_071427.2	Q9H2S6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNMD	ENST00000373031.5	TSL:1 MANE Select	c.577+627C>T		intron	N/A	ENSP00000362122.4	Q9H2S6-1
	ENSG00000301679	ENST00000780746.1		n.77+7910G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.345 AC: 37932 AN: 109946 Hom.: 4913 Cov.: 22

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.374

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.345 AC: 37961 AN: 110000 Hom.: 4919 Cov.: 22 AF XY: 0.339 AC XY: 10953 AN XY: 32300

African (AFR) AF: 0.272 AC: 8230 AN: 30278

American (AMR) AF: 0.442 AC: 4544 AN: 10290

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1009 AN: 2616

East Asian (EAS) AF: 0.662 AC: 2286 AN: 3453

South Asian (SAS) AF: 0.333 AC: 846 AN: 2540

European-Finnish (FIN) AF: 0.329 AC: 1898 AN: 5765

Middle Eastern (MID) AF: 0.386 AC: 81 AN: 210

European-Non Finnish (NFE) AF: 0.346 AC: 18222 AN: 52693

Other (OTH) AF: 0.404 AC: 601 AN: 1488

Alfa AF: 0.337 Hom.: 18677

Bravo AF: 0.359

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.39
DANN	Benign	0.50
PhyloP100		-0.48
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: rs1155974; hg19: chrX-99853281;