20-35917480-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_016436.5(PHF20):c.1826-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00308 in 1,610,546 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (18 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (63 hom.)
• Consequence: PHF20 NM_016436.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001907
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.269

Genes affected

PHF20 (HGNC:16098): (PHD finger protein 20) Predicted to enable DNA binding activity and metal ion binding activity. Involved in histone H4-K16 acetylation; histone H4-K5 acetylation; and histone H4-K8 acetylation. Located in cytosol; nuclear membrane; and nucleoplasm. Part of MLL1 complex and histone acetyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 20-35917480-G-A is Benign according to our data. Variant chr20-35917480-G-A is described in ClinVar as [Benign]. Clinvar id is 786366.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0106 (1614/152132) while in subpopulation EAS AF= 0.0394 (204/5180). AF 95% confidence interval is 0.035. There are 18 homozygotes in gnomad4. There are 797 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1608 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF20	NM_016436.5	c.1826-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000374012.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF20	ENST00000374012.8	c.1826-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_016436.5	P1
PHF20	ENST00000420233.1	c.17-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1608 AN: 152014 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0309

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00538

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0393

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00766

GnomAD3 exomes AF: 0.00542 AC: 1355 AN: 250142 Hom.: 24 AF XY: 0.00452 AC XY: 611 AN XY: 135214

Gnomad AFR exome AF: 0.0312

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0395

Gnomad SAS exome AF: 0.000690

Gnomad FIN exome AF: 0.0000927

Gnomad NFE exome AF: 0.000221

Gnomad OTH exome AF: 0.00442

GnomAD4 exome AF: 0.00229 AC: 3339 AN: 1458414 Hom.: 63 Cov.: 30 AF XY: 0.00212 AC XY: 1540 AN XY: 725646

Gnomad4 AFR exome AF: 0.0316

Gnomad4 AMR exome AF: 0.00209

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0413

Gnomad4 SAS exome AF: 0.000930

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.0000947

Gnomad4 OTH exome AF: 0.00554

GnomAD4 genome AF: 0.0106 AC: 1614 AN: 152132 Hom.: 18 Cov.: 32 AF XY: 0.0107 AC XY: 797 AN XY: 74358

Gnomad4 AFR AF: 0.0310

Gnomad4 AMR AF: 0.00537

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0394

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00456 Hom.: 2

Bravo AF: 0.0116

Asia WGS AF: 0.0380 AC: 130 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 13, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.1
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000019
dbscSNV1_RF	Benign	0.0
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

LitVar

Other links and lift over

dbSNP: rs73618547; hg19: chr20-34505402;