8-132803876-A-G

Variant names:

• chr8-132803876-A-G
• NM_016018.5:c.565A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016018.5(PHF20L1):​c.565A>G​(p.Ser189Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 1.64

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0345591).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF20L1	NM_016018.5	c.565A>G	p.Ser189Gly	missense_variant	Exon 7 of 21	ENST00000395386.7	NP_057102.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF20L1	ENST00000395386.7	c.565A>G	p.Ser189Gly	missense_variant	Exon 7 of 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

May 18, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.565A>G (p.S189G) alteration is located in exon 7 (coding exon 6) of the PHF20L1 gene. This alteration results from a A to G substitution at nucleotide position 565, causing the serine (S) at amino acid position 189 to be replaced by a glycine (G). 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	0.060
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T;T;.;T;.;T;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.78	T;T;T;.;T;T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.035	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;.;.;L;.;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.5	.;.;N;N;N;N;N
REVEL	Benign	0.041
Sift	Uncertain	0.011	.;.;D;D;T;D;T
Sift4G	Benign	0.39	T;T;T;T;T;T;T
Polyphen		0.015	B;.;.;B;B;.;B
Vest4		0.080
MutPred		0.14		Loss of phosphorylation at S189 (P = 0.0113);.;Loss of phosphorylation at S189 (P = 0.0113);Loss of phosphorylation at S189 (P = 0.0113);.;.;.;
MVP		0.19
MPC		0.29
ClinPred		0.11	T
GERP RS		2.0
Varity_R		0.057
gMVP		0.25

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: chr8-133816121;