NM_001424.6:c.*172G>C

Variant names:

• chr16-10532733-C-G
• rs9927921
• NM_001424.6:c.*172G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001424.6(EMP2):​c.*172G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.085 (336 hom., cov: 15)
  • Exomes 𝑓: 0.00056 (15 hom.)
• Consequence: EMP2 NM_001424.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.30
• Publications: 0 publications found

Genes affected

EMP2 (HGNC:3334): (epithelial membrane protein 2) This gene encodes a tetraspan protein of the PMP22/EMP family. The encoded protein regulates cell membrane composition. It has been associated with various functions including endocytosis, cell signaling, cell proliferation, cell migration, cell adhesion, cell death, cholesterol homeostasis, urinary albumin excretion, and embryo implantation. It is known to negatively regulate caveolin-1, a scaffolding protein which is the main component of the caveolae plasma membrane invaginations found in most cell types. Through activation of PTK2 it positively regulates vascular endothelial growth factor A. It also modulates the function of specific integrin isomers in the plasma membrane. Up-regulation of this gene has been linked to cancer progression in multiple different tissues. Mutations in this gene have been associated with nephrotic syndrome type 10 (NPHS10). [provided by RefSeq, Mar 2015]

EMP2 Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 10

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-10532733-C-G is Benign according to our data. Variant chr16-10532733-C-G is described in ClinVar as Benign. ClinVar VariationId is 1266482.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001424.6. 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
	EMP2	NM_001424.6	MANE Select	c.*172G>C		3_prime_UTR	Exon 5 of 5	NP_001415.1	P54851

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMP2	ENST00000359543.8	TSL:1 MANE Select	c.*172G>C		3_prime_UTR	Exon 5 of 5	ENSP00000352540.3	P54851
	EMP2	ENST00000867006.1		c.*172G>C		3_prime_UTR	Exon 5 of 5	ENSP00000537065.1
	EMP2	ENST00000536829.1	TSL:2	c.*172G>C		downstream_gene	N/A	ENSP00000445712.1	P54851

Frequencies

GnomAD3 genomes AF: 0.0850 AC: 4846 AN: 57014 Hom.: 335 Cov.: 15

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0296

Gnomad ASJ AF: 0.000647

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0102

Gnomad NFE AF: 0.000734

Gnomad OTH AF: 0.0365

GnomAD4 exome AF: 0.000562 AC: 236 AN: 419988 Hom.: 15 Cov.: 7 AF XY: 0.000576 AC XY: 119 AN XY: 206736

African (AFR) AF: 0.0253 AC: 206 AN: 8134

American (AMR) AF: 0.000899 AC: 5 AN: 5562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9122

East Asian (EAS) AF: 0.00 AC: 0 AN: 18352

South Asian (SAS) AF: 0.00 AC: 0 AN: 8354

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13050

Middle Eastern (MID) AF: 0.000658 AC: 1 AN: 1520

European-Non Finnish (NFE) AF: 0.0000119 AC: 4 AN: 335704

Other (OTH) AF: 0.000991 AC: 20 AN: 20190

GnomAD4 genome AF: 0.0851 AC: 4853 AN: 57054 Hom.: 336 Cov.: 15 AF XY: 0.0839 AC XY: 2256 AN XY: 26894

African (AFR) AF: 0.241 AC: 4679 AN: 19414

American (AMR) AF: 0.0295 AC: 128 AN: 4334

Ashkenazi Jewish (ASJ) AF: 0.000647 AC: 1 AN: 1546

East Asian (EAS) AF: 0.00 AC: 0 AN: 1838

South Asian (SAS) AF: 0.00 AC: 0 AN: 1788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2530

Middle Eastern (MID) AF: 0.0109 AC: 1 AN: 92

European-Non Finnish (NFE) AF: 0.000734 AC: 18 AN: 24522

Other (OTH) AF: 0.0359 AC: 26 AN: 724

Alfa AF: 0.000263 Hom.: 0

Bravo AF: 0.0433

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.0
DANN	Benign	0.82
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs9927921; hg19: chr16-10626590;