NM_013390.3:c.3956-4_3956-3dupTT

Variant names:

• chr9-71685395-T-TAA
• rs36080695
• NM_013390.3:c.3956-4_3956-3dupTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_013390.3(CEMIP2):​c.3956-4_3956-3dupTT 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 0.27 (5271 hom., cov: 0)
  • Exomes 𝑓: 0.22 (437 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

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.3956-4_3956-3dupTT		splice_region intron	N/A	NP_037522.1	Q9UHN6-1
	CEMIP2	NM_001135820.2		c.3767-4_3767-3dupTT		splice_region intron	N/A	NP_001129292.1	Q9UHN6-2
	CEMIP2	NM_001349784.2		c.2042-4_2042-3dupTT		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_3956-2insTT		splice_region intron	N/A	ENSP00000366243.4	Q9UHN6-1
	CEMIP2	ENST00000377066.9	TSL:1	c.3767-3_3767-2insTT		splice_region intron	N/A	ENSP00000366266.5	Q9UHN6-2
	CEMIP2	ENST00000538669.1	TSL:1	n.1687-3_1687-2insTT		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.274 AC: 31835 AN: 116034 Hom.: 5270 Cov.: 0

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.164

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.244

GnomAD2 exomes AF: 0.125 AC: 2216 AN: 17724 AF XY: 0.123

Gnomad AFR exome AF: 0.229

Gnomad AMR exome AF: 0.164

Gnomad ASJ exome AF: 0.0945

Gnomad EAS exome AF: 0.245

Gnomad FIN exome AF: 0.0703

Gnomad NFE exome AF: 0.0860

Gnomad OTH exome AF: 0.105

GnomAD4 exome AF: 0.216 AC: 221365 AN: 1023208 Hom.: 437 Cov.: 14 AF XY: 0.215 AC XY: 105051 AN XY: 488860

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

African (AFR) AF: 0.365 AC: 7903 AN: 21664

American (AMR) AF: 0.208 AC: 2298 AN: 11026

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 2248 AN: 14364

East Asian (EAS) AF: 0.319 AC: 8035 AN: 25162

South Asian (SAS) AF: 0.214 AC: 6523 AN: 30530

European-Finnish (FIN) AF: 0.219 AC: 5027 AN: 22988

Middle Eastern (MID) AF: 0.180 AC: 508 AN: 2822

European-Non Finnish (NFE) AF: 0.210 AC: 179605 AN: 853234

Other (OTH) AF: 0.223 AC: 9218 AN: 41418

⚠️ 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: 0.274 AC: 31841 AN: 116010 Hom.: 5271 Cov.: 0 AF XY: 0.280 AC XY: 15100 AN XY: 53938

African (AFR) AF: 0.480 AC: 14032 AN: 29220

American (AMR) AF: 0.215 AC: 2291 AN: 10654

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 415 AN: 3082

East Asian (EAS) AF: 0.412 AC: 1722 AN: 4180

South Asian (SAS) AF: 0.261 AC: 907 AN: 3474

European-Finnish (FIN) AF: 0.256 AC: 955 AN: 3736

Middle Eastern (MID) AF: 0.167 AC: 35 AN: 210

European-Non Finnish (NFE) AF: 0.184 AC: 10895 AN: 59102

Other (OTH) AF: 0.248 AC: 381 AN: 1536

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 (auto)

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: COSV65486292;