8-56166533-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002655.3(PLAG1):ā€‹c.1213A>Gā€‹(p.Ile405Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,613,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000039 ( 0 hom., cov: 32)
Exomes š‘“: 0.000027 ( 0 hom. )

Consequence

PLAG1
NM_002655.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0200
Variant links:
Genes affected
PLAG1 (HGNC:9045): (PLAG1 zinc finger) Pleomorphic adenoma gene 1 encodes a zinc finger protein with 2 putative nuclear localization signals. PLAG1, which is developmentally regulated, has been shown to be consistently rearranged in pleomorphic adenomas of the salivary glands. PLAG1 is activated by the reciprocal chromosomal translocations involving 8q12 in a subset of salivary gland pleomorphic adenomas. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.014299899).
BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLAG1NM_002655.3 linkuse as main transcriptc.1213A>G p.Ile405Val missense_variant 5/5 ENST00000316981.8 NP_002646.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLAG1ENST00000316981.8 linkuse as main transcriptc.1213A>G p.Ile405Val missense_variant 5/51 NM_002655.3 ENSP00000325546 P1Q6DJT9-1
PLAG1ENST00000429357.2 linkuse as main transcriptc.1213A>G p.Ile405Val missense_variant 4/41 ENSP00000416537 P1Q6DJT9-1
PLAG1ENST00000522009.1 linkuse as main transcriptn.1664A>G non_coding_transcript_exon_variant 3/31
PLAG1ENST00000423799.6 linkuse as main transcriptc.967A>G p.Ile323Val missense_variant 3/32 ENSP00000404067 Q6DJT9-2

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
152088
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251218
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135804
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.0000868
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000274
AC:
40
AN:
1461738
Hom.:
0
Cov.:
33
AF XY:
0.0000303
AC XY:
22
AN XY:
727176
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000234
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000395
AC:
6
AN:
152088
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74278
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000847
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 03, 2021The c.1213A>G (p.I405V) alteration is located in exon 5 (coding exon 2) of the PLAG1 gene. This alteration results from a A to G substitution at nucleotide position 1213, causing the isoleucine (I) at amino acid position 405 to be replaced by a valine (V). 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
0.082
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
5.3
DANN
Benign
0.37
DEOGEN2
Benign
0.052
T;.;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.052
N
LIST_S2
Benign
0.72
.;T;T
M_CAP
Benign
0.0022
T
MetaRNN
Benign
0.014
T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
-1.1
N;.;N
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.41
T
PROVEAN
Benign
0.30
N;N;N
REVEL
Benign
0.014
Sift
Benign
1.0
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0
B;.;B
Vest4
0.055
MutPred
0.31
Loss of glycosylation at S404 (P = 0.1002);.;Loss of glycosylation at S404 (P = 0.1002);
MVP
0.10
MPC
0.47
ClinPred
0.016
T
GERP RS
-1.1
Varity_R
0.012
gMVP
0.073

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs776708502; hg19: chr8-57079092; COSMIC: COSV57615141; API