rs1114167317

Variant names:

• chr8-56167306-CT-C
• rs1114167317
• NM_002655.3:c.439delA

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_002655.3(PLAG1):​c.439delA​(p.Ser147ValfsTer82) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLAG1 NM_002655.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 3.06
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• silver-russell syndrome 4

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 10 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 8-56167306-CT-C is Pathogenic according to our data. Variant chr8-56167306-CT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 253204.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002655.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAG1	NM_002655.3	MANE Select	c.439delA	p.Ser147ValfsTer82	frameshift	Exon 5 of 5	NP_002646.2	Q6DJT9-1
	PLAG1	NM_001114634.2		c.439delA	p.Ser147ValfsTer82	frameshift	Exon 4 of 4	NP_001108106.1	Q6DJT9-1
	PLAG1	NM_001114635.2		c.193delA	p.Ser65ValfsTer82	frameshift	Exon 3 of 3	NP_001108107.1	Q6DJT9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAG1	ENST00000316981.8	TSL:1 MANE Select	c.439delA	p.Ser147ValfsTer82	frameshift	Exon 5 of 5	ENSP00000325546.3	Q6DJT9-1
	PLAG1	ENST00000429357.2	TSL:1	c.439delA	p.Ser147ValfsTer82	frameshift	Exon 4 of 4	ENSP00000416537.2	Q6DJT9-1
	PLAG1	ENST00000522009.1	TSL:1	n.890delA		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Silver-Russell syndrome 1 (1)
1	-	-	Silver-russell syndrome 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1
Mutation Taster		=1/199	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1114167317;

hg19: chr8-57079865;