NM_013390.3:c.3956-3dupT

Variant names:

• chr9-71685395-T-TA
• rs36080695
• NM_013390.3:c.3956-3dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_013390.3(CEMIP2):​c.3956-3dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (15260 hom., cov: 0)
  • Exomes 𝑓: 0.37 (1402 hom.)
  • Failed GnomAD Quality Control
• Consequence: CEMIP2 NM_013390.3 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 9-71685395-T-TA is Benign according to our data. Variant chr9-71685395-T-TA is described in ClinVar as Benign. ClinVar VariationId is 403552.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.59 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.3956-3dupT		splice_region intron	N/A	NP_037522.1	Q9UHN6-1
	CEMIP2	NM_001135820.2		c.3767-3dupT		splice_region intron	N/A	NP_001129292.1	Q9UHN6-2
	CEMIP2	NM_001349784.2		c.2042-3dupT		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.3956-3dupT		splice_region intron	N/A	ENSP00000366243.4	Q9UHN6-1
	CEMIP2	ENST00000377066.9	TSL:1	c.3767-3dupT		splice_region intron	N/A	ENSP00000366266.5	Q9UHN6-2
	CEMIP2	ENST00000538669.1	TSL:1	n.1687-3dupT		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.514 AC: 59779 AN: 116292 Hom.: 15272 Cov.: 0

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.526

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.541

GnomAD2 exomes AF: 0.248 AC: 4399 AN: 17724 AF XY: 0.235

Gnomad AFR exome AF: 0.267

Gnomad AMR exome AF: 0.301

Gnomad ASJ exome AF: 0.242

Gnomad EAS exome AF: 0.334

Gnomad FIN exome AF: 0.185

Gnomad NFE exome AF: 0.228

Gnomad OTH exome AF: 0.285

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.371 AC: 387930 AN: 1044974 Hom.: 1402 Cov.: 14 AF XY: 0.370 AC XY: 184881 AN XY: 499412

African (AFR) AF: 0.333 AC: 7208 AN: 21674

American (AMR) AF: 0.362 AC: 4119 AN: 11388

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 5200 AN: 14674

East Asian (EAS) AF: 0.399 AC: 10273 AN: 25776

South Asian (SAS) AF: 0.320 AC: 9896 AN: 30878

European-Finnish (FIN) AF: 0.338 AC: 7998 AN: 23654

Middle Eastern (MID) AF: 0.360 AC: 1042 AN: 2892

European-Non Finnish (NFE) AF: 0.375 AC: 326559 AN: 871556

Other (OTH) AF: 0.368 AC: 15635 AN: 42482

GnomAD4 genome AF: 0.514 AC: 59754 AN: 116268 Hom.: 15260 Cov.: 0 AF XY: 0.509 AC XY: 27533 AN XY: 54044

African (AFR) AF: 0.401 AC: 11730 AN: 29280

American (AMR) AF: 0.602 AC: 6427 AN: 10668

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1658 AN: 3082

East Asian (EAS) AF: 0.561 AC: 2354 AN: 4196

South Asian (SAS) AF: 0.497 AC: 1735 AN: 3488

European-Finnish (FIN) AF: 0.470 AC: 1764 AN: 3752

Middle Eastern (MID) AF: 0.510 AC: 107 AN: 210

European-Non Finnish (NFE) AF: 0.552 AC: 32714 AN: 59236

Other (OTH) AF: 0.536 AC: 823 AN: 1536

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs36080695; hg19: chr9-74300311; COSMIC: COSV65486466;