10-91251340-A-T

Position:

• chr10-91251340-A-T

Variant summary

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

The NM_032373.5(PCGF5):​c.374A>T​(p.Glu125Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PCGF5 NM_032373.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.67

Genes affected

PCGF5 (HGNC:28264): (polycomb group ring finger 5) Predicted to enable metal ion binding activity. Acts upstream of or within positive regulation of transcription by RNA polymerase II. Located in Golgi apparatus; centrosome; and nucleoplasm. Part of PcG protein complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.1944713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCGF5	NM_032373.5	c.374A>T	p.Glu125Val	missense_variant	6/10	ENST00000336126.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCGF5	ENST00000336126.6	c.374A>T	p.Glu125Val	missense_variant	6/10	1	NM_032373.5	P1
PCGF5	ENST00000614189.4	c.374A>T	p.Glu125Val	missense_variant	6/10	1		P1
PCGF5	ENST00000543648.5	c.374A>T	p.Glu125Val	missense_variant	6/10	2		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Sep 20, 2023

The c.374A>T (p.E125V) alteration is located in exon 6 (coding exon 5) of the PCGF5 gene. This alteration results from a A to T substitution at nucleotide position 374, causing the glutamic acid (E) at amino acid position 125 to be replaced by a valine (V). 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	0.11
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.059	T;T;T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D;.;.
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.9	.;N;N
REVEL	Benign	0.16
Sift	Benign	0.15	.;T;T
Sift4G	Benign	0.28	T;T;T
Polyphen		0.65	P;P;P
Vest4		0.38
MutPred		0.27		Loss of methylation at K130 (P = 0.1601);Loss of methylation at K130 (P = 0.1601);Loss of methylation at K130 (P = 0.1601);
MVP		0.13
MPC		1.4
ClinPred		0.86	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.49

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-93011097;