chr8-132824010-C-T

Variant names:

• chr8-132824010-C-T
• rs375482501
• NM_016018.5:c.1586C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016018.5(PHF20L1):​c.1586C>T​(p.Ser529Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000017 in 1,588,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: PHF20L1 NM_016018.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.337
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02891004).

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.1586C>T	p.Ser529Leu	missense	Exon 13 of 21	NP_057102.4
	PHF20L1	NM_001438309.1		c.1601C>T	p.Ser534Leu	missense	Exon 13 of 21	NP_001425238.1
	PHF20L1	NM_001438310.1		c.1598C>T	p.Ser533Leu	missense	Exon 13 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.1586C>T	p.Ser529Leu	missense	Exon 13 of 21	ENSP00000378784.2	A8MW92-1
	PHF20L1	ENST00000315808.14	TSL:1	n.1869C>T		non_coding_transcript_exon	Exon 13 of 14
	PHF20L1	ENST00000939789.1		c.1601C>T	p.Ser534Leu	missense	Exon 13 of 21	ENSP00000609848.1

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151446 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000206 AC: 5 AN: 242974 AF XY: 0.0000304

Gnomad AFR exome AF: 0.0000643

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000182

Gnomad OTH exome AF: 0.000171

GnomAD4 exome AF: 0.0000181 AC: 26 AN: 1437444 Hom.: 0 Cov.: 26 AF XY: 0.0000223 AC XY: 16 AN XY: 716234

African (AFR) AF: 0.0000309 AC: 1 AN: 32330

American (AMR) AF: 0.00 AC: 0 AN: 43532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25648

East Asian (EAS) AF: 0.00 AC: 0 AN: 38956

South Asian (SAS) AF: 0.0000236 AC: 2 AN: 84690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 0.0000192 AC: 21 AN: 1093980

Other (OTH) AF: 0.0000337 AC: 2 AN: 59398

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151446 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73930

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000242 AC: 1 AN: 41238

American (AMR) AF: 0.00 AC: 0 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10512

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67804

Other (OTH) AF: 0.00 AC: 0 AN: 2082

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000247 AC: 3

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	Benign	0.053
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	11
DANN	Benign	0.49
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.27	N
PhyloP100		-0.34
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.062
Sift	Benign	0.26	T
Sift4G	Benign	0.33	T
Polyphen		0.0	B
Vest4		0.096
MVP		0.043
MPC		0.25
ClinPred		0.046	T
GERP RS		0.20
Varity_R		0.034
gMVP		0.092
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs375482501; hg19: chr8-133836255; COSMIC: COSV55190320; COSMIC: COSV55190320;