chr9-71694531-C-G

Variant names:

• chr9-71694531-C-G
• rs146520330
• NM_013390.3:c.3674G>C

Variant summary

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

The NM_013390.3(CEMIP2):​c.3674G>C​(p.Arg1225Pro) 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 1,461,550 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1225C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CEMIP2 NM_013390.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376
• Publications: 0 publications found

Genes affected

CEMIP2 (HGNC:11869): (cell migration inducing hyaluronidase 2) This gene encodes a type II transmembrane protein that belongs to the interferon-induced transmembrane (IFITM) protein superfamily. The encoded protein functions as a cell surface hyaluronidase that cleaves extracellular high molecular weight hyaluronan into intermediate size fragments before internalization and degradation in the lysosome. It also has an interferon-mediated antiviral function in humans through activation of the JAK STAT signaling pathway. The activation of this gene by transcription factor SOX4 in breast cancer cells has been shown to mediate the pathological effects of SOX4 on cancer progression. Naturally occurring mutations in this gene are associated with autosomal recessive non-syndromic hearing loss. [provided by RefSeq, Mar 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013390.3. 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
	CEMIP2	NM_013390.3	MANE Select	c.3674G>C	p.Arg1225Pro	missense	Exon 21 of 24	NP_037522.1	Q9UHN6-1
	CEMIP2	NM_001135820.2		c.3485G>C	p.Arg1162Pro	missense	Exon 20 of 23	NP_001129292.1	Q9UHN6-2
	CEMIP2	NM_001349784.2		c.1760G>C	p.Arg587Pro	missense	Exon 21 of 24	NP_001336713.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEMIP2	ENST00000377044.9	TSL:1 MANE Select	c.3674G>C	p.Arg1225Pro	missense	Exon 21 of 24	ENSP00000366243.4	Q9UHN6-1
	CEMIP2	ENST00000377066.9	TSL:1	c.3485G>C	p.Arg1162Pro	missense	Exon 20 of 23	ENSP00000366266.5	Q9UHN6-2
	CEMIP2	ENST00000542935.5	TSL:1	n.*1897G>C		non_coding_transcript_exon	Exon 21 of 24	ENSP00000437750.1	F5H6B2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251254 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461550 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727100

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.0000224 AC: 1 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111782

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.044
Eigen_PC	Benign	0.049
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.60	T
PhyloP100		0.38
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.19
Sift	Benign	0.070	T
Sift4G	Benign	0.18	T
Polyphen		0.79	P
Vest4		0.62
MutPred		0.19		Gain of glycosylation at S1229 (P = 0.0843)
MVP		0.69
MPC		0.35
ClinPred		0.85	D
GERP RS		5.3
Varity_R		0.41
gMVP		0.77
Mutation Taster		=74/26	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: rs146520330; hg19: chr9-74309447;