6-143941495-G-A

Position:

• chr6-143941495-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001317162.2(PLAGL1):​c.1321C>T​(p.Pro441Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLAGL1 NM_001317162.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.36

Genes affected

PLAGL1 (HGNC:9046): (PLAG1 like zinc finger 1) This gene encodes a C2H2 zinc finger protein that functions as a suppressor of cell growth. This gene is often deleted or methylated and silenced in cancer cells. In addition, overexpression of this gene during fetal development is thought to be the causal factor for transient neonatal diabetes mellitus (TNDM). Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding two different protein isoforms. The P1 downstream promoter of this gene is imprinted, with preferential expression from the paternal allele in many tissues. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.065072894).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAGL1	NM_001317162.2	c.1321C>T	p.Pro441Ser	missense_variant	8/8	ENST00000674357.1	NP_001304091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAGL1	ENST00000674357.1	c.1321C>T	p.Pro441Ser	missense_variant	8/8		NM_001317162.2	ENSP00000501459	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Myoepithelial tumor Uncertain:1

Uncertain significance, no assertion criteria provided

research

Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine

Nov 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.52
DEOGEN2	Benign	0.16	T;T;.;T;T;.;T;T;.;T;T;.;T;.
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.55
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.79	.;.;T;.;.;T;T;.;.;.;.;.;.;.
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.065	T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.88	L;L;.;L;L;.;L;L;.;L;L;.;L;.
MutationTaster	Benign	0.77	N;N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.98	N;.;.;N;N;N;N;.;N;.;.;.;N;.
REVEL	Benign	0.075
Sift	Benign	0.73	T;.;.;T;T;T;T;.;T;.;.;.;T;.
Sift4G	Benign	0.94	T;.;T;T;T;T;T;.;T;T;.;.;T;T
Polyphen		0.0060	B;B;.;B;B;.;B;B;.;B;B;.;B;.
Vest4		0.063
MutPred		0.20		Loss of catalytic residue at P440 (P = 0.0677);Loss of catalytic residue at P440 (P = 0.0677);.;Loss of catalytic residue at P440 (P = 0.0677);Loss of catalytic residue at P440 (P = 0.0677);.;Loss of catalytic residue at P440 (P = 0.0677);Loss of catalytic residue at P440 (P = 0.0677);.;Loss of catalytic residue at P440 (P = 0.0677);Loss of catalytic residue at P440 (P = 0.0677);.;Loss of catalytic residue at P440 (P = 0.0677);.;
MVP		0.16
MPC		0.42
ClinPred		0.17	T
GERP RS		4.8
Varity_R		0.085
gMVP		0.31

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.

Other links and lift over

hg19: chr6-144262632;