15-80873955-C-T

Variant names:

• chr15-80873955-C-T
• rs757101934
• NM_001293298.2:c.76C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001293298.2(CEMIP):​c.76C>T​(p.Pro26Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000282 in 1,419,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: CEMIP NM_001293298.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.739
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02514705).

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.76C>T	p.Pro26Ser	missense	Exon 3 of 30	NP_001280227.1	Q8WUJ3-1
	CEMIP	NM_001293304.2		c.76C>T	p.Pro26Ser	missense	Exon 3 of 30	NP_001280233.1	Q8WUJ3-1
	CEMIP	NM_018689.3		c.76C>T	p.Pro26Ser	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.76C>T	p.Pro26Ser	missense	Exon 3 of 30	ENSP00000378177.3	Q8WUJ3-1
	CEMIP	ENST00000220244.7	TSL:1	c.76C>T	p.Pro26Ser	missense	Exon 2 of 29	ENSP00000220244.3	Q8WUJ3-1
	CEMIP	ENST00000356249.9	TSL:1	c.76C>T	p.Pro26Ser	missense	Exon 3 of 30	ENSP00000348583.5	Q8WUJ3-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000541 AC: 1 AN: 184922 AF XY: 0.0000102

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000367

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000282 AC: 4 AN: 1419516 Hom.: 0 Cov.: 30 AF XY: 0.00000285 AC XY: 2 AN XY: 701660

African (AFR) AF: 0.00 AC: 0 AN: 33128

American (AMR) AF: 0.0000260 AC: 1 AN: 38406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25256

East Asian (EAS) AF: 0.00 AC: 0 AN: 38372

South Asian (SAS) AF: 0.0000248 AC: 2 AN: 80750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50464

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

European-Non Finnish (NFE) AF: 9.19e-7 AC: 1 AN: 1088612

Other (OTH) AF: 0.00 AC: 0 AN: 58810

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000844 AC: 1

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	-0.60
CADD	Benign	0.46
DANN	Benign	0.29
DEOGEN2	Benign	0.064	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.74
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.38	N
REVEL	Benign	0.088
Sift	Benign	0.36	T
Sift4G	Benign	0.13	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.38		Gain of catalytic residue at P26 (P = 0.002)
MVP		0.18
MPC		0.37
ClinPred		0.048	T
GERP RS		0.52
Varity_R		0.020
gMVP		0.49
Mutation Taster		=96/4	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: rs757101934; hg19: chr15-81166296;