15-80880917-A-G

Position:

• chr15-80880917-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001293298.2(CEMIP):​c.398A>G​(p.Gln133Arg) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CEMIP NM_001293298.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.773

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, CEMIP
• BP4: Computational evidence support a benign effect (MetaRNN=0.13240495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEMIP	NM_001293298.2	c.398A>G	p.Gln133Arg	missense_variant	6/30	ENST00000394685.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEMIP	ENST00000394685.8	c.398A>G	p.Gln133Arg	missense_variant	6/30	1	NM_001293298.2	P1
CEMIP	ENST00000220244.7	c.398A>G	p.Gln133Arg	missense_variant	5/29	1		P1
CEMIP	ENST00000356249.9	c.398A>G	p.Gln133Arg	missense_variant	6/30	1		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 22, 2024

The c.398A>G (p.Q133R) alteration is located in exon 5 (coding exon 4) of the CEMIP gene. This alteration results from a A to G substitution at nucleotide position 398, causing the glutamine (Q) at amino acid position 133 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	7.0
DANN	Benign	0.78
DEOGEN2	Benign	0.25	T;T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.31	N
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.2	L;L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.24
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.35	T;T;T
Polyphen		0.049	B;B;B
Vest4		0.28
MutPred		0.45		Gain of disorder (P = 0.233);Gain of disorder (P = 0.233);Gain of disorder (P = 0.233);
MVP		0.43
MPC		0.49
ClinPred		0.050	T
GERP RS		-2.0
Varity_R		0.062
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-81173258; COSMIC: COSV104527620;