8-132794784-T-C

Variant names:

• chr8-132794784-T-C
• NM_016018.5:c.307T>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016018.5(PHF20L1):​c.307T>C​(p.Tyr103His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHF20L1 NM_016018.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.804

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF20L1	NM_016018.5	c.307T>C	p.Tyr103His	missense_variant	Exon 4 of 21	ENST00000395386.7	NP_057102.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF20L1	ENST00000395386.7	c.307T>C	p.Tyr103His	missense_variant	Exon 4 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

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.307T>C (p.Y103H) alteration is located in exon 4 (coding exon 3) of the PHF20L1 gene. This alteration results from a T to C substitution at nucleotide position 307, causing the tyrosine (Y) at amino acid position 103 to be replaced by a histidine (H). 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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D;T;.;D;.;.;T;.;T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;D;.;D;D;D;D;D
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.80	D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.15	T
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-4.7	.;.;D;D;.;D;D;D;D
REVEL	Pathogenic	0.73
Sift	Pathogenic	0.0	.;.;D;D;.;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D;D
Polyphen		0.99	D;.;D;D;.;D;.;.;D
Vest4		0.94
MutPred		0.56		Gain of methylation at K106 (P = 0.0548);Gain of methylation at K106 (P = 0.0548);Gain of methylation at K106 (P = 0.0548);Gain of methylation at K106 (P = 0.0548);Gain of methylation at K106 (P = 0.0548);Gain of methylation at K106 (P = 0.0548);Gain of methylation at K106 (P = 0.0548);.;Gain of methylation at K106 (P = 0.0548);
MVP		0.71
MPC		2.6
ClinPred		0.99	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.72
gMVP		0.85

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-133807030; COSMIC: COSV55197520; COSMIC: COSV55197520;