rs777379448

Variant names:

• chr8-8318164-T-A
• rs777379448
• NM_001080826.3:c.4211A>T

Your query was ambiguous. Multiple possible variants found:

• chr8-8318164-T-A
• chr8-8318164-T-C

Variant summary

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

The NM_001080826.3(PRAG1):​c.4211A>T​(p.Gln1404Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. Q1404R) 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: 6.18
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRAG1	NM_001080826.3	c.4211A>T	p.Gln1404Leu	missense_variant	Exon 6 of 6	ENST00000615670.5	NP_001074295.2
PRAG1	NM_001369759.1	c.4211A>T	p.Gln1404Leu	missense_variant	Exon 6 of 6		NP_001356688.1
PRAG1	NR_163138.1	n.4508A>T		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.4211A>T	p.Gln1404Leu	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	Uncertain	0.35
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.32	T;.
M_CAP	Benign	0.0095	T
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-0.84	T
PhyloP100		6.2
PrimateAI	Uncertain	0.68	T
Sift4G	Uncertain	0.025	D;D
Vest4		0.65
MVP		0.32
ClinPred		0.91	D
GERP RS		4.3
Varity_R		0.21
gMVP		0.23
Mutation Taster		=100/0	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: rs777379448; hg19: chr8-8175686; COSMIC: COSV58160556;