Genetic Variant ASPRV1:p.Pro230Thr (chr2-69960749-G-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP5

The NM_152792.4(ASPRV1):c.688C>A(p.Pro230Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ASPRV1
NM_152792.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.55

Publications

0 publications found

Variant links:

Genes affected

ASPRV1 (HGNC:26321): (aspartic peptidase retroviral like 1) Filaggrin is a structural protein that is crucial for in the development and maintenance of the skin barrier. This gene encodes a retroviral-like protease involved in profilaggrin-to-filaggrin processing. Expression is found primarily in the epidermis and inner root sheath of hair follicles. [provided by RefSeq, May 2017]

ASPRV1 Gene-Disease associations (from GenCC):

ichthyosis, lamellar, autosomal dominant
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics, G2P

ASPRV1 links:

ENSG00000293615 (HGNC:):

ENSG00000293615 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 2-69960749-G-T is Pathogenic according to our data. Variant chr2-69960749-G-T is described in ClinVar as Pathogenic. ClinVar VariationId is 977278.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152792.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASPRV1	NM_152792.4	MANE Select	c.688C>A	p.Pro230Thr	missense	Exon 1 of 1	NP_690005.3	Q53RT3-2
ASPRV1	NR_170631.1		n.3231C>A		non_coding_transcript_exon	Exon 5 of 5
ASPRV1	NR_170632.1		n.3381C>A		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASPRV1	ENST00000320256.6	TSL:6 MANE Select	c.688C>A	p.Pro230Thr	missense	Exon 1 of 1	ENSP00000315383.5	Q53RT3-2
ENSG00000293615	ENST00000419542.6	TSL:5	c.940C>A	p.Pro314Thr	missense	Exon 6 of 6	ENSP00000520552.1
ENSG00000293615	ENST00000630975.4	TSL:5	c.940C>A	p.Pro314Thr	missense	Exon 7 of 7	ENSP00000520555.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal dominant lamellar ichthyosis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Uncertain

0.074

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.63

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.63

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.60

MutationAssessor

Benign

0.97

PhyloP100

2.6

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.19

Sift

Benign

0.043

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.28

MutPred

0.40

Gain of phosphorylation at P314 (P = 0.0495)

MVP

0.61

MPC

0.54

ClinPred

0.96

GERP RS

5.4

Varity_R

0.17

gMVP

0.44

Mutation Taster

=77/23

disease causing (ClinVar)

(source)

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over