8-8318869-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001080826.3(PRAG1):c.3506C>A(p.Ala1169Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 4/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1169S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 0)
• Consequence: PRAG1 NM_001080826.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30

Genes affected

PRAG1 (HGNC:25438): (PEAK1 related, kinase-activating pseudokinase 1) This gene encodes an enzyme that belongs to the tyrosine protein kinase family. A similar protein in rat binds to Rho family GTPase 2 (Rnd2) and regulates neurite outgrowth via activation of Ras homolog gene family, member A (RhoA). [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.105029196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRAG1	NM_001080826.3	c.3506C>A	p.Ala1169Asp	missense_variant	6/6	ENST00000615670.5
PRAG1	NM_001369759.1	c.3506C>A	p.Ala1169Asp	missense_variant	6/6
PRAG1	NR_163138.1	n.3803C>A		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRAG1	ENST00000615670.5	c.3506C>A	p.Ala1169Asp	missense_variant	6/6	5	NM_001080826.3	P1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2024

The c.3494C>A (p.A1165D) alteration is located in exon 5 (coding exon 5) of the SGK223 gene. This alteration results from a C to A substitution at nucleotide position 3494, causing the alanine (A) at amino acid position 1165 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	Benign	0.16
Cadd	Benign	8.9
DEOGEN2	Benign	0.0049	T;T
LIST_S2	Benign	0.21	T;.
MetaRNN	Benign	0.11	T;T
Sift4G	Benign	0.15	T;T
Vest4		0.27
gMVP		0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1798375728; hg19: -;