chr20-23047619-C-A

Variant names:

• chr20-23047619-C-A
• rs3176121
• NM_000361.3:c.*158G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000361.3(THBD):​c.*158G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: THBD NM_000361.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• Publications: 1 publications found

Genes affected

THBD (HGNC:11784): (thrombomodulin) The protein encoded by this intronless gene is an endothelial-specific type I membrane receptor that binds thrombin. This binding results in the activation of protein C, which degrades clotting factors Va and VIIIa and reduces the amount of thrombin generated. Mutations in this gene are a cause of thromboembolic disease, also known as inherited thrombophilia. [provided by RefSeq, Jul 2008]

THBD Gene-Disease associations (from GenCC):

• atypical hemolytic-uremic syndrome with thrombomodulin anomaly

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• thrombomodulin-related bleeding disorder

  Inheritance: AR, AD, Unknown Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ENSG00000296483 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000361.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBD	NM_000361.3	MANE Select	c.*158G>T		3_prime_UTR	Exon 1 of 1	NP_000352.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBD	ENST00000377103.3	TSL:6 MANE Select	c.*158G>T		3_prime_UTR	Exon 1 of 1	ENSP00000366307.2
	ENSG00000296483	ENST00000739851.1		n.795+3200G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 718038 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 363536

African (AFR) AF: 0.00 AC: 0 AN: 17494

American (AMR) AF: 0.00 AC: 0 AN: 20128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15480

East Asian (EAS) AF: 0.00 AC: 0 AN: 32222

South Asian (SAS) AF: 0.00 AC: 0 AN: 51474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2488

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 514100

Other (OTH) AF: 0.00 AC: 0 AN: 34830

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.3
DANN	Benign	0.51
PhyloP100		0.042

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: rs3176121; hg19: chr20-23028256;