20-35917475-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_016436.5(PHF20):c.1826-9T>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00082 in 1,611,050 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00047 (2 hom.)
• Consequence: PHF20 NM_016436.5 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.01533
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.55

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 20-35917475-T-G is Benign according to our data. Variant chr20-35917475-T-G is described in ClinVar as [Benign]. Clinvar id is 710868.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 611 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF20	NM_016436.5	c.1826-9T>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000374012.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF20	ENST00000374012.8	c.1826-9T>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_016436.5	P1
PHF20	ENST00000420233.1	c.17-9T>G		splice_polypyrimidine_tract_variant, intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00401 AC: 611 AN: 152236 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00108 AC: 270 AN: 249602 Hom.: 0 AF XY: 0.000749 AC XY: 101 AN XY: 134934

Gnomad AFR exome AF: 0.0149

Gnomad AMR exome AF: 0.000613

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000660

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.000469 AC: 684 AN: 1458696 Hom.: 2 Cov.: 30 AF XY: 0.000413 AC XY: 300 AN XY: 725746

Gnomad4 AFR exome AF: 0.0153

Gnomad4 AMR exome AF: 0.000809

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000582

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000433

Gnomad4 OTH exome AF: 0.00129

GnomAD4 genome AF: 0.00418 AC: 637 AN: 152354 Hom.: 7 Cov.: 32 AF XY: 0.00401 AC XY: 299 AN XY: 74502

Gnomad4 AFR AF: 0.0144

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00190 Hom.: 0

Bravo AF: 0.00475

Asia WGS AF: 0.00202 AC: 7 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

Jun 18, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	14
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.015
dbscSNV1_RF	Benign	0.13
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

LitVar

Other links and lift over

dbSNP: rs139713561; hg19: chr20-34505397;