15-80929151-C-G

Variant names:

• chr15-80929151-C-G
• NM_001293298.2:c.2589C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001293298.2(CEMIP):​c.2589C>G​(p.Ser863Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CEMIP NM_001293298.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.91

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]

ENSG00000259546 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039719522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEMIP	NM_001293298.2	c.2589C>G	p.Ser863Arg	missense_variant	Exon 21 of 30	ENST00000394685.8	NP_001280227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEMIP	ENST00000394685.8	c.2589C>G	p.Ser863Arg	missense_variant	Exon 21 of 30	1	NM_001293298.2	ENSP00000378177.3
CEMIP	ENST00000220244.7	c.2589C>G	p.Ser863Arg	missense_variant	Exon 20 of 29	1		ENSP00000220244.3
CEMIP	ENST00000356249.9	c.2589C>G	p.Ser863Arg	missense_variant	Exon 21 of 30	1		ENSP00000348583.5
ENSG00000259546	ENST00000560873.1	n.173-19399G>C		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.0020
DANN	Benign	0.61
DEOGEN2	Benign	0.057	T;T;T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.82	.;.;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.040	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.23	N;N;N
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.090	N;N;N
REVEL	Benign	0.076
Sift	Benign	0.39	T;T;T
Sift4G	Benign	0.61	T;T;T
Polyphen		0.015	B;B;B
Vest4		0.32
MutPred		0.32		Loss of glycosylation at S863 (P = 0.0357);Loss of glycosylation at S863 (P = 0.0357);Loss of glycosylation at S863 (P = 0.0357);
MVP		0.092
MPC		0.44
ClinPred		0.27	T
GERP RS		-9.7
Varity_R		0.11
gMVP		0.80

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: chr15-81221492;