chr4-154546163-C-T

Variant names:

• chr4-154546163-C-T
• rs368289009
• NM_002669.4:c.364G>A

Variant summary

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

The NM_002669.4(PLRG1):​c.364G>A​(p.Ala122Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,457,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PLRG1 NM_002669.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.58

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=0.21231285).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLRG1	NM_002669.4	c.364G>A	p.Ala122Thr	missense_variant	Exon 5 of 15	ENST00000499023.7	NP_002660.1
PLRG1	NM_001201564.2	c.337G>A	p.Ala113Thr	missense_variant	Exon 5 of 15		NP_001188493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLRG1	ENST00000499023.7	c.364G>A	p.Ala122Thr	missense_variant	Exon 5 of 15	1	NM_002669.4	ENSP00000424417.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251288 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135824

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457256 Hom.: 0 Cov.: 27 AF XY: 0.00000138 AC XY: 1 AN XY: 725322

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.094	T;.;T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.0	M;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.12	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.28	T;T;D
Sift4G	Benign	0.40	T;T;.
Polyphen		0.040	B;P;.
Vest4		0.18
MutPred		0.19		Loss of sheet (P = 0.0084);.;.;
MVP		0.37
MPC		0.43
ClinPred		0.46	T
GERP RS		5.9
Varity_R		0.12
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs368289009; hg19: chr4-155467315;