chr8-8318189-G-T

Variant names:

• chr8-8318189-G-T
• rs1377164539
• NM_001080826.3:c.4186C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080826.3(PRAG1):​c.4186C>A​(p.Leu1396Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L1396F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRAG1 NM_001080826.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.15
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2612368).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRAG1	NM_001080826.3	c.4186C>A	p.Leu1396Ile	missense_variant	Exon 6 of 6	ENST00000615670.5	NP_001074295.2
PRAG1	NM_001369759.1	c.4186C>A	p.Leu1396Ile	missense_variant	Exon 6 of 6		NP_001356688.1
PRAG1	NR_163138.1	n.4483C>A		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRAG1	ENST00000615670.5	c.4186C>A	p.Leu1396Ile	missense_variant	Exon 6 of 6	5	NM_001080826.3	ENSP00000481109.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.038	T;T
Eigen	Benign	0.14
Eigen_PC	Benign	0.075
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.30	T;.
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.53	T
PhyloP100		4.1
PrimateAI	Uncertain	0.59	T
Sift4G	Uncertain	0.022	D;D
Vest4		0.39
MVP		0.15
ClinPred		0.77	D
GERP RS		3.6
Varity_R		0.44
gMVP		0.26
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1377164539; hg19: chr8-8175711;