8-132817032-T-C

Position:

• chr8-132817032-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016018.5(PHF20L1):​c.1328T>C​(p.Phe443Ser) 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: 5.19

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]

PHF20L1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28593892).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF20L1	NM_016018.5	c.1328T>C	p.Phe443Ser	missense_variant	11/21	ENST00000395386.7	NP_057102.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHF20L1	ENST00000395386.7	c.1328T>C	p.Phe443Ser	missense_variant	11/21	5	NM_016018.5	ENSP00000378784.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Jun 07, 2023

The c.1328T>C (p.F443S) alteration is located in exon 11 (coding exon 10) of the PHF20L1 gene. This alteration results from a T to C substitution at nucleotide position 1328, causing the phenylalanine (F) at amino acid position 443 to be replaced by a serine (S). 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	0.29
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	T;T;T;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T;T;.;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.0	L;.;L;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.17	.;.;N;N
REVEL	Benign	0.19
Sift	Pathogenic	0.0	.;.;D;D
Sift4G	Benign	0.47	T;T;T;T
Polyphen		1.0	D;.;D;D
Vest4		0.49
MutPred		0.087		Gain of phosphorylation at F443 (P = 0.0129);.;Gain of phosphorylation at F443 (P = 0.0129);.;
MVP		0.082
MPC		0.51
ClinPred		0.76	D
GERP RS		5.3
Varity_R		0.42
gMVP		0.34

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-133829277;