chr10-7563220-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_030569.7(ITIH5):c.2692G>C(p.Gly898Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
ITIH5
NM_030569.7 missense
NM_030569.7 missense
Scores
4
7
4
Clinical Significance
Conservation
PhyloP100: 7.46
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITIH5 | NM_030569.7 | c.2692G>C | p.Gly898Arg | missense_variant | 14/14 | ENST00000397146.7 | |
ITIH5 | NM_032817.6 | c.2050G>C | p.Gly684Arg | missense_variant | 10/10 | ||
ITIH5 | XM_011519713.4 | c.2767G>C | p.Gly923Arg | missense_variant | 15/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITIH5 | ENST00000397146.7 | c.2692G>C | p.Gly898Arg | missense_variant | 14/14 | 1 | NM_030569.7 | P1 | |
ITIH5 | ENST00000613909.4 | c.2050G>C | p.Gly684Arg | missense_variant | 10/10 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 35
GnomAD4 exome
Cov.:
35
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 22, 2023 | The c.2692G>C (p.G898R) alteration is located in exon 14 (coding exon 14) of the ITIH5 gene. This alteration results from a G to C substitution at nucleotide position 2692, causing the glycine (G) at amino acid position 898 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D
Vest4
MutPred
Gain of MoRF binding (P = 0.0222);.;
MVP
ClinPred
D
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.