15-80873959-G-A

Variant names:

• chr15-80873959-G-A
• rs781104409
• NM_001293298.2:c.80G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001293298.2(CEMIP):​c.80G>A​(p.Gly27Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000917 in 1,571,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000096 (0 hom.)
• Consequence: CEMIP NM_001293298.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.470
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09608343).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001293298.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEMIP	NM_001293298.2	MANE Select	c.80G>A	p.Gly27Glu	missense	Exon 3 of 30	NP_001280227.1	Q8WUJ3-1
	CEMIP	NM_001293304.2		c.80G>A	p.Gly27Glu	missense	Exon 3 of 30	NP_001280233.1	Q8WUJ3-1
	CEMIP	NM_018689.3		c.80G>A	p.Gly27Glu	missense	Exon 2 of 29	NP_061159.1	Q8WUJ3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEMIP	ENST00000394685.8	TSL:1 MANE Select	c.80G>A	p.Gly27Glu	missense	Exon 3 of 30	ENSP00000378177.3	Q8WUJ3-1
	CEMIP	ENST00000220244.7	TSL:1	c.80G>A	p.Gly27Glu	missense	Exon 2 of 29	ENSP00000220244.3	Q8WUJ3-1
	CEMIP	ENST00000356249.9	TSL:1	c.80G>A	p.Gly27Glu	missense	Exon 3 of 30	ENSP00000348583.5	Q8WUJ3-1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152152 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000706 AC: 13 AN: 184094 AF XY: 0.0000514

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000111

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000105

Gnomad OTH exome AF: 0.000410

GnomAD4 exome AF: 0.0000958 AC: 136 AN: 1418930 Hom.: 0 Cov.: 30 AF XY: 0.0000827 AC XY: 58 AN XY: 701344

African (AFR) AF: 0.0000604 AC: 2 AN: 33108

American (AMR) AF: 0.000131 AC: 5 AN: 38290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25250

East Asian (EAS) AF: 0.00 AC: 0 AN: 38364

South Asian (SAS) AF: 0.00 AC: 0 AN: 80730

European-Finnish (FIN) AF: 0.0000198 AC: 1 AN: 50408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.000115 AC: 125 AN: 1088270

Other (OTH) AF: 0.0000510 AC: 3 AN: 58792

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152152 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74334

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68026

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.000132 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000253 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	14
DANN	Benign	0.79
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.47
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.077
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.64	T
Polyphen		0.0	B
Vest4		0.19
MutPred		0.43		Gain of solvent accessibility (P = 0.005)
MVP		0.22
MPC		0.51
ClinPred		0.062	T
GERP RS		2.3
Varity_R		0.13
gMVP		0.54
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs781104409; hg19: chr15-81166300;