Genetic Variant NM_013390.3:c.3956-6_3956-3dupTTTT (chr9-71685395-T-TAAAA) – ACMG Classification: Uncertain_significance (0 pts)

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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.302

Publications

3 publications found

Variant links:

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]

CEMIP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEMIP2	NM_013390.3 link	c.3956-6_3956-3dupTTTT		splice_region_variant, intron_variant	Intron 23 of 23	ENST00000377044.9	NP_037522.1	Q9UHN6-1A0A024R229

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEMIP2	ENST00000377044.9 link	c.3956-3_3956-2insTTTT		splice_region_variant, intron_variant	Intron 23 of 23	1	NM_013390.3	ENSP00000366243.4		Q9UHN6-1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

116348

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

Cov.:

AF XY:

0.00270

AC XY:

1365

AN XY:

505974

show subpopulations

⚠️ 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:

AN:

11492

Ashkenazi Jewish (ASJ)

AF:

0.00300

AC:

AN:

14984

East Asian (EAS)

AF:

0.00203

AC:

AN:

26048

South Asian (SAS)

AF:

0.00863

AC:

268

AN:

31058

European-Finnish (FIN)

AF:

0.00203

AC:

AN:

24092

Middle Eastern (MID)

AF:

0.00102

AC:

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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.296

Heterozygous variant carriers

250

500

749

999

1249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000155

AC:

AN:

116324

Hom.:

Cov.:

AF XY:

0.000203

AC XY:

AN XY:

54084

show subpopulations

African (AFR)

AF:

0.0000683

AC:

AN:

29284

American (AMR)

AF:

0.00

AC:

AN:

10664

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3084

East Asian (EAS)

AF:

0.000238

AC:

AN:

4194

South Asian (SAS)

AF:

0.000287

AC:

AN:

3486

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3756

Middle Eastern (MID)

AF:

0.00

AC:

AN:

210

European-Non Finnish (NFE)

AF:

0.000169

AC:

AN:

59288

Other (OTH)

AF:

0.00260

AC:

AN:

1540

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.30

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over