9-71685395-TAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAA

Variant names:

• chr9-71685395-T-TAAAA
• rs36080695
• NM_013390.3:c.3956-6_3956-3dupTTTT

Variant summary

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

The NM_013390.3(CEMIP2):​c.3956-6_3956-3dupTTTT 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 0.00015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0027 (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.3956-6_3956-3dupTTTT		splice_region intron	N/A	NP_037522.1	Q9UHN6-1
	CEMIP2	NM_001135820.2		c.3767-6_3767-3dupTTTT		splice_region intron	N/A	NP_001129292.1	Q9UHN6-2
	CEMIP2	NM_001349784.2		c.2042-6_2042-3dupTTTT		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_3956-2insTTTT		splice_region intron	N/A	ENSP00000366243.4	Q9UHN6-1
	CEMIP2	ENST00000377066.9	TSL:1	c.3767-3_3767-2insTTTT		splice_region intron	N/A	ENSP00000366266.5	Q9UHN6-2
	CEMIP2	ENST00000538669.1	TSL:1	n.1687-3_1687-2insTTTT		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 16 AN: 116348 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000684

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000237

Gnomad SAS AF: 0.000285

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000169

Gnomad OTH AF: 0.00130

GnomAD2 exomes AF: 0.00824 AC: 146 AN: 17724 AF XY: 0.00786

Gnomad AFR exome AF: 0.0113

Gnomad AMR exome AF: 0.00611

Gnomad ASJ exome AF: 0.00762

Gnomad EAS exome AF: 0.0154

Gnomad FIN exome AF: 0.00351

Gnomad NFE exome AF: 0.00738

Gnomad OTH exome AF: 0.0110

GnomAD4 exome AF: 0.00274 AC: 2905 AN: 1058464 Hom.: 1 Cov.: 14 AF XY: 0.00270 AC XY: 1365 AN XY: 505974

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

African (AFR) AF: 0.00673 AC: 148 AN: 21994

American (AMR) AF: 0.00339 AC: 39 AN: 11492

Ashkenazi Jewish (ASJ) AF: 0.00300 AC: 45 AN: 14984

East Asian (EAS) AF: 0.00203 AC: 53 AN: 26048

South Asian (SAS) AF: 0.00863 AC: 268 AN: 31058

European-Finnish (FIN) AF: 0.00203 AC: 49 AN: 24092

Middle Eastern (MID) AF: 0.00102 AC: 3 AN: 2936

European-Non Finnish (NFE) AF: 0.00247 AC: 2182 AN: 882770

Other (OTH) AF: 0.00274 AC: 118 AN: 43090

⚠️ 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: 0.000155 AC: 18 AN: 116324 Hom.: 0 Cov.: 0 AF XY: 0.000203 AC XY: 11 AN XY: 54084

African (AFR) AF: 0.0000683 AC: 2 AN: 29284

American (AMR) AF: 0.00 AC: 0 AN: 10664

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

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

South Asian (SAS) AF: 0.000287 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: 0.000169 AC: 10 AN: 59288

Other (OTH) AF: 0.00260 AC: 4 AN: 1540

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism

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; COSMIC: COSV65489541;