8-8318870-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001080826.3(PRAG1):c.3505G>T(p.Ala1169Ser) 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. A1169D) 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: -0.702

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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05991906).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRAG1	NM_001080826.3	c.3505G>T	p.Ala1169Ser	missense_variant	6/6	ENST00000615670.5
PRAG1	NM_001369759.1	c.3505G>T	p.Ala1169Ser	missense_variant	6/6
PRAG1	NR_163138.1	n.3802G>T		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRAG1	ENST00000615670.5	c.3505G>T	p.Ala1169Ser	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

Aug 19, 2023

The c.3493G>T (p.A1165S) alteration is located in exon 5 (coding exon 5) of the SGK223 gene. This alteration results from a G to T substitution at nucleotide position 3493, causing the alanine (A) at amino acid position 1165 to be replaced by a serine (S). 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	0.077
Cadd	Benign	0.30
DEOGEN2	Benign	0.0039	T;T
LIST_S2	Benign	0.22	T;.
MetaRNN	Benign	0.060	T;T
Sift4G	Benign	1.0	T;T
Vest4		0.14
gMVP		0.36

Splicing

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: -;