Variant chr15-80880968-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The ENST00000394685.8(CEMIP):c.449C>T(p.Ala150Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CEMIP
ENST00000394685.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00

Variant links:

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]

CEMIP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 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.

BP4

Computational evidence support a benign effect (MetaRNN=0.21749854).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEMIP	NM_001293298.2 linkuse as main transcript	c.449C>T	p.Ala150Val	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 linkuse as main transcript	c.449C>T	p.Ala150Val	missense_variant	6/30	1	NM_001293298.2	ENSP00000378177	P1	Q8WUJ3-1
CEMIP	ENST00000220244.7 linkuse as main transcript	c.449C>T	p.Ala150Val	missense_variant	5/29	1		ENSP00000220244	P1	Q8WUJ3-1
CEMIP	ENST00000356249.9 linkuse as main transcript	c.449C>T	p.Ala150Val	missense_variant	6/30	1		ENSP00000348583	P1	Q8WUJ3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251434

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Athena Diagnostics

Feb 11, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.22

T;T;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.81

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.23

.;.;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

-0.81

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.61

PROVEAN

Benign

0.32

N;N;N

REVEL

Benign

0.25

Sift

Benign

0.031

D;D;D

Sift4G

Benign

0.10

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.28

MutPred

0.45

Loss of disorder (P = 0.0783);Loss of disorder (P = 0.0783);Loss of disorder (P = 0.0783);

MVP

0.29

MPC

0.36

ClinPred

0.16

GERP RS

2.5

Varity_R

0.036

gMVP

0.54

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over