8-132794471-C-G

Variant names:

• chr8-132794471-C-G
• rs747048371
• NM_016018.5:c.145C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016018.5(PHF20L1):​c.145C>G​(p.Arg49Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,940 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R49C) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: PHF20L1 NM_016018.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 2 publications found

Genes affected

PHF20L1 (HGNC:24280): (PHD finger protein 20 like 1) Predicted to enable metal ion binding activity. Predicted to be involved in histone acetylation and regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of NSL complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016018.5. 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
	PHF20L1	NM_016018.5	MANE Select	c.145C>G	p.Arg49Gly	missense	Exon 3 of 21	NP_057102.4
	PHF20L1	NM_001438309.1		c.145C>G	p.Arg49Gly	missense	Exon 3 of 21	NP_001425238.1
	PHF20L1	NM_001438310.1		c.145C>G	p.Arg49Gly	missense	Exon 3 of 21	NP_001425239.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF20L1	ENST00000395386.7	TSL:5 MANE Select	c.145C>G	p.Arg49Gly	missense	Exon 3 of 21	ENSP00000378784.2	A8MW92-1
	PHF20L1	ENST00000337920.8	TSL:1	c.145C>G	p.Arg49Gly	missense	Exon 3 of 8	ENSP00000338269.4	A8MW92-2
	PHF20L1	ENST00000315808.14	TSL:1	n.428C>G		non_coding_transcript_exon	Exon 3 of 14

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151940 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151940 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74194

African (AFR) AF: 0.00 AC: 0 AN: 41348

American (AMR) AF: 0.00 AC: 0 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67982

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	-0.090	N
PhyloP100		7.9
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.35
Sift	Benign	0.14	T
Sift4G	Uncertain	0.0060	D
Polyphen		0.092	B
Vest4		0.53
MutPred		0.56		Loss of MoRF binding (P = 0.0094)
MVP		0.14
MPC		2.6
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.83
gMVP		0.89
Mutation Taster		=13/87	disease causing

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

Other links and lift over

dbSNP: rs747048371; hg19: chr8-133806717;