9-71685395-TAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr9-71685395-T-TAAAAAAAAAAAA
• rs36080695
• NM_013390.3:c.3956-14_3956-3dupTTTTTTTTTTTT

Variant summary

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

The NM_013390.3(CEMIP2):​c.3956-14_3956-3dupTTTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000069 (0 hom.)
• Consequence: CEMIP2 NM_013390.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302
• Publications: 3 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 0 ACMG points.

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.3956-14_3956-3dupTTTTTTTTTTTT		splice_region intron	N/A	NP_037522.1	Q9UHN6-1
	CEMIP2	NM_001135820.2		c.3767-14_3767-3dupTTTTTTTTTTTT		splice_region intron	N/A	NP_001129292.1	Q9UHN6-2
	CEMIP2	NM_001349784.2		c.2042-14_2042-3dupTTTTTTTTTTTT		splice_region intron	N/A	NP_001336713.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEMIP2	ENST00000377044.9	TSL:1 MANE Select	c.3956-14_3956-3dupTTTTTTTTTTTT		splice_region intron	N/A	ENSP00000366243.4	Q9UHN6-1
	CEMIP2	ENST00000377066.9	TSL:1	c.3767-14_3767-3dupTTTTTTTTTTTT		splice_region intron	N/A	ENSP00000366266.5	Q9UHN6-2
	CEMIP2	ENST00000538669.1	TSL:1	n.1687-14_1687-3dupTTTTTTTTTTTT		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000860 AC: 10 AN: 116342 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000205

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000237

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000266

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000337

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000687 AC: 73 AN: 1062532 Hom.: 0 Cov.: 14 AF XY: 0.0000768 AC XY: 39 AN XY: 507876

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000225 AC: 5 AN: 22246

American (AMR) AF: 0.000346 AC: 4 AN: 11548

Ashkenazi Jewish (ASJ) AF: 0.000133 AC: 2 AN: 15040

East Asian (EAS) AF: 0.000458 AC: 12 AN: 26190

South Asian (SAS) AF: 0.000256 AC: 8 AN: 31242

European-Finnish (FIN) AF: 0.0000827 AC: 2 AN: 24176

Middle Eastern (MID) AF: 0.000339 AC: 1 AN: 2954

European-Non Finnish (NFE) AF: 0.0000418 AC: 37 AN: 885904

Other (OTH) AF: 0.0000463 AC: 2 AN: 43232

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000860 AC: 10 AN: 116318 Hom.: 0 Cov.: 0 AF XY: 0.000129 AC XY: 7 AN XY: 54080

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000205 AC: 6 AN: 29274

American (AMR) AF: 0.00 AC: 0 AN: 10662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3084

East Asian (EAS) AF: 0.000238 AC: 1 AN: 4194

South Asian (SAS) AF: 0.00 AC: 0 AN: 3486

European-Finnish (FIN) AF: 0.000266 AC: 1 AN: 3756

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 210

European-Non Finnish (NFE) AF: 0.0000337 AC: 2 AN: 59294

Other (OTH) AF: 0.00 AC: 0 AN: 1540

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs36080695; hg19: chr9-74300311;