2-69961243-A-T

Position:

• chr2-69961243-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152792.4(ASPRV1):​c.194T>A​(p.Val65Asp) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ASPRV1 NM_152792.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.848

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]

PCBP1-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33852494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASPRV1	NM_152792.4	c.194T>A	p.Val65Asp	missense_variant	1/1	ENST00000320256.6	NP_690005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASPRV1	ENST00000320256.6	c.194T>A	p.Val65Asp	missense_variant	1/1	6	NM_152792.4	ENSP00000315383.5
PCBP1-AS1	ENST00000682294.1	n.3620T>A		non_coding_transcript_exon_variant	8/8			ENSP00000520553.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 01, 2024

The c.446T>A (p.V149D) alteration is located in exon 1 (coding exon 1) of the ASPRV1 gene. This alteration results from a T to A substitution at nucleotide position 446, causing the valine (V) at amino acid position 149 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Benign	0.83
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.18
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.74	P
Vest4		0.47
MutPred		0.42		Gain of disorder (P = 0.0063);
MVP		0.48
MPC		0.58
ClinPred		0.53	D
GERP RS		-0.84
Varity_R		0.14
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-70188375;