9-71685395-TAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr9-71685395-T-TAAAAAAA
• rs36080695
• NM_013390.3:c.3956-9_3956-3dupTTTTTTT

Variant summary

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

The NM_013390.3(CEMIP2):​c.3956-9_3956-3dupTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00066 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00032 (1 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.3956-9_3956-3dupTTTTTTT		splice_region intron	N/A	NP_037522.1	Q9UHN6-1
	CEMIP2	NM_001135820.2		c.3767-9_3767-3dupTTTTTTT		splice_region intron	N/A	NP_001129292.1	Q9UHN6-2
	CEMIP2	NM_001349784.2		c.2042-9_2042-3dupTTTTTTT		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.3956-3_3956-2insTTTTTTT		splice_region intron	N/A	ENSP00000366243.4	Q9UHN6-1
	CEMIP2	ENST00000377066.9	TSL:1	c.3767-3_3767-2insTTTTTTT		splice_region intron	N/A	ENSP00000366266.5	Q9UHN6-2
	CEMIP2	ENST00000538669.1	TSL:1	n.1687-3_1687-2insTTTTTTT		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000655 AC: 76 AN: 115946 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000480

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000376

Gnomad ASJ AF: 0.00131

Gnomad EAS AF: 0.00143

Gnomad SAS AF: 0.000285

Gnomad FIN AF: 0.000533

Gnomad MID AF: 0.00439

Gnomad NFE AF: 0.000728

Gnomad OTH AF: 0.000654

GnomAD2 exomes AF: 0.00564 AC: 100 AN: 17724 AF XY: 0.00584

Gnomad AFR exome AF: 0.00644

Gnomad AMR exome AF: 0.00376

Gnomad ASJ exome AF: 0.0122

Gnomad EAS exome AF: 0.0140

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00499

Gnomad OTH exome AF: 0.0110

GnomAD4 exome AF: 0.000321 AC: 341 AN: 1062164 Hom.: 1 Cov.: 14 AF XY: 0.000355 AC XY: 180 AN XY: 507688

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

African (AFR) AF: 0.000360 AC: 8 AN: 22234

American (AMR) AF: 0.00122 AC: 14 AN: 11522

Ashkenazi Jewish (ASJ) AF: 0.000798 AC: 12 AN: 15034

East Asian (EAS) AF: 0.000994 AC: 26 AN: 26160

South Asian (SAS) AF: 0.00218 AC: 68 AN: 31174

European-Finnish (FIN) AF: 0.000373 AC: 9 AN: 24158

Middle Eastern (MID) AF: 0.000677 AC: 2 AN: 2954

European-Non Finnish (NFE) AF: 0.000213 AC: 189 AN: 885708

Other (OTH) AF: 0.000301 AC: 13 AN: 43220

⚠️ 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: 0.000656 AC: 76 AN: 115924 Hom.: 0 Cov.: 0 AF XY: 0.000650 AC XY: 35 AN XY: 53886

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

African (AFR) AF: 0.000479 AC: 14 AN: 29210

American (AMR) AF: 0.000376 AC: 4 AN: 10634

Ashkenazi Jewish (ASJ) AF: 0.00131 AC: 4 AN: 3064

East Asian (EAS) AF: 0.00143 AC: 6 AN: 4186

South Asian (SAS) AF: 0.000287 AC: 1 AN: 3480

European-Finnish (FIN) AF: 0.000533 AC: 2 AN: 3754

Middle Eastern (MID) AF: 0.00481 AC: 1 AN: 208

European-Non Finnish (NFE) AF: 0.000728 AC: 43 AN: 59036

Other (OTH) AF: 0.000652 AC: 1 AN: 1534

⚠️ 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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs36080695; hg19: chr9-74300311;