rs138437547

Variant names:

• chr2-69960957-C-A
• rs138437547
• NM_152792.4:c.480G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-69960957-C-A
• chr2-69960957-C-G
• chr2-69960957-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152792.4(ASPRV1):​c.480G>T​(p.Lys160Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K160K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ASPRV1 NM_152792.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300
• Publications: 0 publications found

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

ENSG00000293615 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2992469).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASPRV1	NM_152792.4	MANE Select	c.480G>T	p.Lys160Asn	missense	Exon 1 of 1	NP_690005.3	Q53RT3-2
	ASPRV1	NR_170631.1		n.3023G>T		non_coding_transcript_exon	Exon 5 of 5
	ASPRV1	NR_170632.1		n.3173G>T		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASPRV1	ENST00000320256.6	TSL:6 MANE Select	c.480G>T	p.Lys160Asn	missense	Exon 1 of 1	ENSP00000315383.5	Q53RT3-2
	ENSG00000293615	ENST00000419542.6	TSL:5	c.732G>T	p.Lys244Asn	missense	Exon 6 of 6	ENSP00000520552.1
	ENSG00000293615	ENST00000630975.4	TSL:5	c.732G>T	p.Lys244Asn	missense	Exon 7 of 7	ENSP00000520555.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Benign	0.055
Eigen_PC	Benign	0.00056
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.030
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.19
Sift	Uncertain	0.017	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.18
MutPred		0.56		Loss of methylation at K244 (P = 0.0106)
MVP		0.54
MPC		0.55
ClinPred		0.90	D
GERP RS		-0.048
Varity_R		0.14
gMVP		0.54
Mutation Taster		=66/34	polymorphism

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: rs138437547; hg19: chr2-70188089; COSMIC: COSV100208443; COSMIC: COSV100208443;