Genetic Variant PHF21A:c.1685-4_1685-3delTT (chr11-45935741-TAA-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001352027.3(PHF21A):c.1685-4_1685-3delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 517,128 control chromosomes in the GnomAD database, including 44 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.017 ( 20 hom., cov: 0)

Exomes 𝑓: 0.20 ( 24 hom. )

Consequence

PHF21A
NM_001352027.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.117

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 -10 ACMG points.

BP6

Variant 11-45935741-TAA-T is Benign according to our data. Variant chr11-45935741-TAA-T is described in ClinVar as [Benign]. Clinvar id is 403295.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-45935741-TAA-T is described in Lovd as [Likely_benign].

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF21A	NM_001352027.3 link	c.1685-4_1685-3delTT		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.1685-4_1685-3delTT		splice_region_variant, intron_variant	Intron 17 of 18		NM_001352027.3	ENSP00000502222.1		Q96BD5-3

Frequencies

GnomAD3 genomes

AF:

0.0173

AC:

1876

AN:

108330

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0316

Gnomad AMI

AF:

0.00273

Gnomad AMR

AF:

0.00824

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.00617

Gnomad SAS

AF:

0.0163

Gnomad FIN

AF:

0.0118

Gnomad MID

AF:

0.0169

Gnomad NFE

AF:

0.0131

Gnomad OTH

AF:

0.0132

GnomAD3 exomes

AF:

0.115

AC:

5550

AN:

48272

Hom.:

AF XY:

0.109

AC XY:

2766

AN XY:

25422

show subpopulations

Gnomad AFR exome

AF:

0.0974

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.0933

Gnomad EAS exome

AF:

0.164

Gnomad SAS exome

AF:

0.100

Gnomad FIN exome

AF:

0.0487

Gnomad NFE exome

AF:

0.103

Gnomad OTH exome

AF:

0.130

GnomAD4 exome

AF:

0.199

AC:

81154

AN:

408786

Hom.:

AF XY:

0.195

AC XY:

42138

AN XY:

215876

show subpopulations

Gnomad4 AFR exome

AF:

0.188

Gnomad4 AMR exome

AF:

0.168

Gnomad4 ASJ exome

AF:

0.184

Gnomad4 EAS exome

AF:

0.204

Gnomad4 SAS exome

AF:

0.158

Gnomad4 FIN exome

AF:

0.197

Gnomad4 NFE exome

AF:

0.207

Gnomad4 OTH exome

AF:

0.203

GnomAD4 genome

AF:

0.0173

AC:

1876

AN:

108342

Hom.:

Cov.:

AF XY:

0.0174

AC XY:

875

AN XY:

50172

show subpopulations

Gnomad4 AFR

AF:

0.0315

Gnomad4 AMR

AF:

0.00833

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.00618

Gnomad4 SAS

AF:

0.0157

Gnomad4 FIN

AF:

0.0118

Gnomad4 NFE

AF:

0.0131

Gnomad4 OTH

AF:

0.0139

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

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

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

11-45935741-TAAAAAAAAAAAAAA-TAAAAAAAAAAAA

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