10-91261332-A-T

Variant names:

• chr10-91261332-A-T
• rs200475271
• NM_032373.5:c.481A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032373.5(PCGF5):​c.481A>T​(p.Met161Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M161V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PCGF5 NM_032373.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.95
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29959688).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032373.5. 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
	PCGF5	NM_032373.5	MANE Select	c.481A>T	p.Met161Leu	missense	Exon 7 of 10	NP_115749.2
	PCGF5	NM_001256549.2		c.481A>T	p.Met161Leu	missense	Exon 7 of 10	NP_001243478.1	Q86SE9-1
	PCGF5	NM_001257101.2		c.481A>T	p.Met161Leu	missense	Exon 7 of 10	NP_001244030.1	Q86SE9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCGF5	ENST00000336126.6	TSL:1 MANE Select	c.481A>T	p.Met161Leu	missense	Exon 7 of 10	ENSP00000337500.5	Q86SE9-1
	PCGF5	ENST00000614189.4	TSL:1	c.481A>T	p.Met161Leu	missense	Exon 7 of 10	ENSP00000479492.1	Q86SE9-1
	PCGF5	ENST00000543648.5	TSL:2	c.481A>T	p.Met161Leu	missense	Exon 7 of 10	ENSP00000445704.1	Q86SE9-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
PhyloP100		8.9
Varity_R		0.45
gMVP		0.62
Mutation Taster		=62/38	polymorphism

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

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

Other links and lift over

dbSNP: rs200475271; hg19: chr10-93021089;