rs370516592

Variant names:

• chr8-8318171-G-A
• rs370516592
• NM_001080826.3:c.4204C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-8318171-G-A
• chr8-8318171-G-C

Variant summary

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

The NM_001080826.3(PRAG1):​c.4204C>T​(p.Leu1402Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,460,990 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L1402V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PRAG1 NM_001080826.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.47

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.4204C>T	p.Leu1402Phe	missense_variant	Exon 6 of 6	ENST00000615670.5	NP_001074295.2
PRAG1	NM_001369759.1	c.4204C>T	p.Leu1402Phe	missense_variant	Exon 6 of 6		NP_001356688.1
PRAG1	NR_163138.1	n.4501C>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.4204C>T	p.Leu1402Phe	missense_variant	Exon 6 of 6	5	NM_001080826.3	ENSP00000481109.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460990 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726796

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111648

Other (OTH) AF: 0.00 AC: 0 AN: 60344

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.052	T;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.44	T;.
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.50	D;D
MetaSVM	Uncertain	-0.21	T
PhyloP100		6.5
PrimateAI	Uncertain	0.68	T
Sift4G	Uncertain	0.014	D;D
Vest4		0.55
MVP		0.27
ClinPred		0.87	D
GERP RS		5.5
Varity_R		0.61
gMVP		0.31
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

Publications

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Other links and lift over

dbSNP: rs370516592; hg19: chr8-8175693;