chr4-154545871-C-G

Position:

• chr4-154545871-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002669.4(PLRG1):​c.457G>C​(p.Ala153Pro) 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 (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLRG1 NM_002669.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.493

Genes affected

PLRG1 (HGNC:9089): (pleiotropic regulator 1) This gene encodes a core component of the cell division cycle 5-like (CDC5L) complex. The CDC5L complex is part of the spliceosome and is required for pre-mRNA splicing. The encoded protein plays a critical role in alternative splice site selection. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07496694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLRG1	NM_002669.4	c.457G>C	p.Ala153Pro	missense_variant	6/15	ENST00000499023.7	NP_002660.1
PLRG1	NM_001201564.2	c.430G>C	p.Ala144Pro	missense_variant	6/15		NP_001188493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLRG1	ENST00000499023.7	c.457G>C	p.Ala153Pro	missense_variant	6/15	1	NM_002669.4	ENSP00000424417	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 03, 2023

The c.457G>C (p.A153P) alteration is located in exon 6 (coding exon 6) of the PLRG1 gene. This alteration results from a G to C substitution at nucleotide position 457, causing the alanine (A) at amino acid position 153 to be replaced by a proline (P). 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	0.086
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.075	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.16	N;N;N
REVEL	Benign	0.076
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.17	T;T;.
Polyphen		0.0	B;P;.
Vest4		0.17
MutPred		0.19		Gain of sheet (P = 0.0061);.;.;
MVP		0.46
MPC		0.34
ClinPred		0.25	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.044
gMVP		0.23

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: chr4-155467023;