Variant 8-56166591-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002655.3(PLAG1):c.1155T>G(p.Asp385Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,702 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PLAG1
NM_002655.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0720

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]

PLAG1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.054505497).

BP6

Variant 8-56166591-A-C is Benign according to our data. Variant chr8-56166591-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2333592.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAG1	NM_002655.3 linkuse as main transcript	c.1155T>G	p.Asp385Glu	missense_variant	5/5	ENST00000316981.8	NP_002646.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAG1	ENST00000316981.8 linkuse as main transcript	c.1155T>G	p.Asp385Glu	missense_variant	5/5	1	NM_002655.3	ENSP00000325546	P1	Q6DJT9-1
PLAG1	ENST00000429357.2 linkuse as main transcript	c.1155T>G	p.Asp385Glu	missense_variant	4/4	1		ENSP00000416537	P1	Q6DJT9-1
PLAG1	ENST00000522009.1 linkuse as main transcript	n.1606T>G		non_coding_transcript_exon_variant	3/3	1
PLAG1	ENST00000423799.6 linkuse as main transcript	c.909T>G	p.Asp303Glu	missense_variant	3/3	2		ENSP00000404067		Q6DJT9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461702

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.1

DANN

Benign

0.93

DEOGEN2

Benign

0.059

T;.;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.67

.;T;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.055

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.20

N;.;N

MutationTaster

Benign

0.89

D;D;D

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.13

N;N;N

REVEL

Benign

0.067

Sift

Benign

0.41

T;T;T

Sift4G

Benign

0.74

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.045

MutPred

0.28

Gain of catalytic residue at D385 (P = 0.2606);.;Gain of catalytic residue at D385 (P = 0.2606);

MVP

0.11

MPC

0.52

ClinPred

0.23

GERP RS

-4.1

Varity_R

0.061

gMVP

0.068

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over