9-71685395-TAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr9-71685395-T-TAAAAAAAAAAA
• rs36080695
• NM_013390.3:c.3956-13_3956-3dupTTTTTTTTTTT

Variant summary

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

The NM_013390.3(CEMIP2):​c.3956-13_3956-3dupTTTTTTTTTTT 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 0.00028 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00014 (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.3956-13_3956-3dupTTTTTTTTTTT		splice_region intron	N/A	NP_037522.1	Q9UHN6-1
	CEMIP2	NM_001135820.2		c.3767-13_3767-3dupTTTTTTTTTTT		splice_region intron	N/A	NP_001129292.1	Q9UHN6-2
	CEMIP2	NM_001349784.2		c.2042-13_2042-3dupTTTTTTTTTTT		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.3956-13_3956-3dupTTTTTTTTTTT		splice_region intron	N/A	ENSP00000366243.4	Q9UHN6-1
	CEMIP2	ENST00000377066.9	TSL:1	c.3767-13_3767-3dupTTTTTTTTTTT		splice_region intron	N/A	ENSP00000366266.5	Q9UHN6-2
	CEMIP2	ENST00000538669.1	TSL:1	n.1687-13_1687-3dupTTTTTTTTTTT		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000284 AC: 33 AN: 116320 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000513

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000938

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000475

Gnomad SAS AF: 0.000285

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000219

Gnomad OTH AF: 0.000652

GnomAD4 exome AF: 0.000139 AC: 148 AN: 1062490 Hom.: 0 Cov.: 14 AF XY: 0.000187 AC XY: 95 AN XY: 507848

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

African (AFR) AF: 0.000450 AC: 10 AN: 22246

American (AMR) AF: 0.000693 AC: 8 AN: 11546

Ashkenazi Jewish (ASJ) AF: 0.000399 AC: 6 AN: 15038

East Asian (EAS) AF: 0.000955 AC: 25 AN: 26190

South Asian (SAS) AF: 0.000896 AC: 28 AN: 31234

European-Finnish (FIN) AF: 0.000165 AC: 4 AN: 24172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2954

European-Non Finnish (NFE) AF: 0.0000689 AC: 61 AN: 885878

Other (OTH) AF: 0.000139 AC: 6 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: 0.000284 AC: 33 AN: 116296 Hom.: 0 Cov.: 0 AF XY: 0.000277 AC XY: 15 AN XY: 54070

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

African (AFR) AF: 0.000512 AC: 15 AN: 29272

American (AMR) AF: 0.0000938 AC: 1 AN: 10658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3082

East Asian (EAS) AF: 0.000477 AC: 2 AN: 4192

South Asian (SAS) AF: 0.000287 AC: 1 AN: 3486

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3756

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

European-Non Finnish (NFE) AF: 0.000219 AC: 13 AN: 59284

Other (OTH) AF: 0.000649 AC: 1 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;