rs193920741

Variant names:

• chr10-7563367-C-A
• rs193920741
• NM_030569.7:c.2545G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030569.7(ITIH5):​c.2545G>T​(p.Asp849Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITIH5 NM_030569.7 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 5.75
• Publications: 1 publications found

Genes affected

ITIH5 (HGNC:21449): (inter-alpha-trypsin inhibitor heavy chain 5) This gene encodes a heavy chain component of one of the inter-alpha-trypsin inhibitor (ITI) family members. ITI proteins are involved in extracellular matrix stabilization and in the prevention of tumor metastasis. They are also structurally related plasma serine protease inhibitors and are composed of a light chain and varying numbers of heavy chains. This family member is thought to function as a tumor suppressor in breast and thyroid cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2999728).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030569.7. 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
	ITIH5	NM_030569.7	MANE Select	c.2545G>T	p.Asp849Tyr	missense	Exon 14 of 14	NP_085046.5
	ITIH5	NM_032817.6		c.1903G>T	p.Asp635Tyr	missense	Exon 10 of 10	NP_116206.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITIH5	ENST00000397146.7	TSL:1 MANE Select	c.2545G>T	p.Asp849Tyr	missense	Exon 14 of 14	ENSP00000380333.3	C9J2H1
	ITIH5	ENST00000613909.4	TSL:1	c.1903G>T	p.Asp635Tyr	missense	Exon 10 of 10	ENSP00000485414.1	A0A096LP62
	ITIH5	ENST00000884049.1		c.2620G>T	p.Asp874Tyr	missense	Exon 15 of 15	ENSP00000554108.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.95	T
PhyloP100		5.8
PrimateAI	Benign	0.35	T
Sift4G	Uncertain	0.0080	D
Vest4		0.28
MutPred		0.58		Loss of relative solvent accessibility (P = 0.008)
MVP		0.44
ClinPred		0.97	D
GERP RS		5.0
gMVP		0.64
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs193920741; hg19: chr10-7605330; COSMIC: COSV53675171; COSMIC: COSV53675171;