Genetic Variant PHF21A:c.1685-7_1685-3delTTTTT (chr11-45935741-TAAAAA-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_001352027.3(PHF21A):c.1685-7_1685-3delTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 515,874 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.000065 ( 0 hom., cov: 0)

Exomes 𝑓: 0.017 ( 0 hom. )

Consequence

PHF21A
NM_001352027.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.62

Variant links:

Genes affected

PHF21A (HGNC:24156): (PHD finger protein 21A) The PHF21A gene encodes BHC80, a component of a BRAF35 (MIM 605535)/histone deacetylase (HDAC; see MIM 601241) complex (BHC) that mediates repression of neuron-specific genes through the cis-regulatory element known as repressor element-1 (RE1) or neural restrictive silencer (NRS) (Hakimi et al., 2002 [PubMed 12032298]).[supplied by OMIM, Nov 2010]

PHF21A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 11-45935741-TAAAAA-T is Benign according to our data. Variant chr11-45935741-TAAAAA-T is described in ClinVar as [Benign]. Clinvar id is 3041678.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0174 (7082/407538) while in subpopulation AMR AF= 0.0199 (329/16564). AF 95% confidence interval is 0.0181. There are 0 homozygotes in gnomad4_exome. There are 3803 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF21A	NM_001352027.3 link	c.1685-7_1685-3delTTTTT		splice_region_variant, intron_variant	Intron 17 of 18	ENST00000676320.1	NP_001338956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF21A	ENST00000676320.1 link	c.1685-7_1685-3delTTTTT		splice_region_variant, intron_variant	Intron 17 of 18		NM_001352027.3	ENSP00000502222.1		Q96BD5-3

Frequencies

GnomAD3 genomes

AF:

0.0000646

AC:

AN:

108336

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000350

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000388

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000186

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0148

AC:

716

AN:

48272

Hom.:

AF XY:

0.0157

AC XY:

398

AN XY:

25422

show subpopulations

Gnomad AFR exome

AF:

0.00924

Gnomad AMR exome

AF:

0.0231

Gnomad ASJ exome

AF:

0.0133

Gnomad EAS exome

AF:

0.0185

Gnomad SAS exome

AF:

0.0142

Gnomad FIN exome

AF:

0.00853

Gnomad NFE exome

AF:

0.0132

Gnomad OTH exome

AF:

0.0195

GnomAD4 exome

AF:

0.0174

AC:

7082

AN:

407538

Hom.:

AF XY:

0.0177

AC XY:

3803

AN XY:

215236

show subpopulations

Gnomad4 AFR exome

AF:

0.0159

Gnomad4 AMR exome

AF:

0.0199

Gnomad4 ASJ exome

AF:

0.0179

Gnomad4 EAS exome

AF:

0.0168

Gnomad4 SAS exome

AF:

0.0163

Gnomad4 FIN exome

AF:

0.0164

Gnomad4 NFE exome

AF:

0.0175

Gnomad4 OTH exome

AF:

0.0181

GnomAD4 genome

AF:

0.0000646

AC:

AN:

108336

Hom.:

Cov.:

AF XY:

0.0000598

AC XY:

AN XY:

50148

show subpopulations

Gnomad4 AFR

AF:

0.0000350

Gnomad4 AMR

AF:

0.000388

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.0000186

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PHF21A-related disorder

Benign:1

Jan 13, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

11-45935741-TAAAAAAAAAAAAAA-TAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over