8-132814666-A-C

Variant names:

• chr8-132814666-A-C
• rs900975487
• NM_016018.5:c.960A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016018.5(PHF20L1):​c.960A>C​(p.Lys320Asn) variant causes a missense change. 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: PHF20L1 NM_016018.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.77
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18594882).

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.960A>C	p.Lys320Asn	missense	Exon 10 of 21	NP_057102.4
	PHF20L1	NM_001438309.1		c.975A>C	p.Lys325Asn	missense	Exon 10 of 21	NP_001425238.1
	PHF20L1	NM_001438310.1		c.972A>C	p.Lys324Asn	missense	Exon 10 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.960A>C	p.Lys320Asn	missense	Exon 10 of 21	ENSP00000378784.2	A8MW92-1
	PHF20L1	ENST00000315808.14	TSL:1	n.1243A>C		non_coding_transcript_exon	Exon 10 of 14
	PHF20L1	ENST00000939789.1		c.975A>C	p.Lys325Asn	missense	Exon 10 of 21	ENSP00000609848.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.69
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.8
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.098
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.094	T
Polyphen		1.0	D
Vest4		0.36
MutPred		0.22		Loss of methylation at K320 (P = 0.0021)
MVP		0.14
MPC		0.93
ClinPred		0.79	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.53
Mutation Taster		=81/19	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

Other links and lift over

dbSNP: rs900975487; hg19: chr8-133826911;