rs200475271

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr10-91261332-A-G
• chr10-91261332-A-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_032373.5(PCGF5):​c.481A>G​(p.Met161Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000394 in 1,499,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (0 hom.)
• Consequence: PCGF5 NM_032373.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12172988).
• BS2: High AC in GnomAd4 at 32 AD gene.

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>G	p.Met161Val	missense	Exon 7 of 10	NP_115749.2
	PCGF5	NM_001256549.2		c.481A>G	p.Met161Val	missense	Exon 7 of 10	NP_001243478.1	Q86SE9-1
	PCGF5	NM_001257101.2		c.481A>G	p.Met161Val	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>G	p.Met161Val	missense	Exon 7 of 10	ENSP00000337500.5	Q86SE9-1
	PCGF5	ENST00000614189.4	TSL:1	c.481A>G	p.Met161Val	missense	Exon 7 of 10	ENSP00000479492.1	Q86SE9-1
	PCGF5	ENST00000543648.5	TSL:2	c.481A>G	p.Met161Val	missense	Exon 7 of 10	ENSP00000445704.1	Q86SE9-1

Frequencies

GnomAD3 genomes AF: 0.000210 AC: 32 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000294 AC: 66 AN: 224148 AF XY: 0.000286

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000394

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000475

Gnomad NFE exome AF: 0.000526

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000415 AC: 559 AN: 1347508 Hom.: 0 Cov.: 30 AF XY: 0.000415 AC XY: 275 AN XY: 662160

African (AFR) AF: 0.00 AC: 0 AN: 30916

American (AMR) AF: 0.00 AC: 0 AN: 35098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23356

East Asian (EAS) AF: 0.00 AC: 0 AN: 37772

South Asian (SAS) AF: 0.000394 AC: 26 AN: 65924

European-Finnish (FIN) AF: 0.0000203 AC: 1 AN: 49192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5336

European-Non Finnish (NFE) AF: 0.000496 AC: 518 AN: 1045138

Other (OTH) AF: 0.000256 AC: 14 AN: 54776

GnomAD4 genome AF: 0.000210 AC: 32 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74472

African (AFR) AF: 0.0000721 AC: 3 AN: 41588

American (AMR) AF: 0.000262 AC: 4 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000257 Hom.: 0

Bravo AF: 0.000249

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000468 AC: 4

ExAC AF: 0.000338 AC: 41

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Uncertain	0.020
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.086	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		8.9
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.26
Sift	Benign	0.15	T
Sift4G	Benign	0.28	T
Polyphen		0.17	B
Vest4		0.62
MVP		0.61
MPC		1.7
ClinPred		0.11	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.40
gMVP		0.72
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

dbSNP: rs200475271; hg19: chr10-93021089; COSMIC: COSV99075852;