chr15-80880950-G-C
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP2PP3_Strong
The NM_001293298.2(CEMIP):āc.431G>Cā(p.Gly144Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000082 ( 0 hom. )
Consequence
CEMIP
NM_001293298.2 missense
NM_001293298.2 missense
Scores
5
8
6
Clinical Significance
Conservation
PhyloP100: 8.49
Genes affected
CEMIP (HGNC:29213): (cell migration inducing hyaluronidase 1) Enables several functions, including clathrin heavy chain binding activity; hyaluronic acid binding activity; and hyalurononglucosaminidase activity. Involved in several processes, including hyaluronan catabolic process; positive regulation of protein phosphorylation; and positive regulation of transport. Located in clathrin-coated endocytic vesicle; endoplasmic reticulum; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CEMIP. . Gene score misZ 1.6603 (greater than the threshold 3.09). Trascript score misZ 3.3078 (greater than threshold 3.09). GenCC has associacion of gene with nonsyndromic genetic hearing loss.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.974
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CEMIP | NM_001293298.2 | c.431G>C | p.Gly144Ala | missense_variant | 6/30 | ENST00000394685.8 | NP_001280227.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CEMIP | ENST00000394685.8 | c.431G>C | p.Gly144Ala | missense_variant | 6/30 | 1 | NM_001293298.2 | ENSP00000378177 | P1 | |
CEMIP | ENST00000220244.7 | c.431G>C | p.Gly144Ala | missense_variant | 5/29 | 1 | ENSP00000220244 | P1 | ||
CEMIP | ENST00000356249.9 | c.431G>C | p.Gly144Ala | missense_variant | 6/30 | 1 | ENSP00000348583 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461888Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727246
GnomAD4 exome
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12
AN:
1461888
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32
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AC XY:
7
AN XY:
727246
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
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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 | Jan 20, 2023 | The c.431G>C (p.G144A) alteration is located in exon 5 (coding exon 4) of the CEMIP gene. This alteration results from a G to C substitution at nucleotide position 431, causing the glycine (G) at amino acid position 144 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;D;D
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;.;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Pathogenic
Sift
Benign
D;D;D
Sift4G
Benign
T;T;T
Polyphen
D;D;D
Vest4
MutPred
Loss of ubiquitination at K147 (P = 0.0863);Loss of ubiquitination at K147 (P = 0.0863);Loss of ubiquitination at K147 (P = 0.0863);
MVP
MPC
1.2
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at