11-45935741-TAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAA

Position:

• chr11-45935741-TAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001352027.3(PHF21A):​c.1685-3dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.012 (20 hom., cov: 0)
  • Exomes 𝑓: 0.0094 (0 hom.)
• Consequence: PHF21A NM_001352027.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1274/108314) while in subpopulation AFR AF= 0.0392 (1122/28604). AF 95% confidence interval is 0.0373. There are 20 homozygotes in gnomad4. There are 594 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1274 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF21A	NM_001352027.3	c.1685-3dupT		splice_region_variant, intron_variant		ENST00000676320.1	NP_001338956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHF21A	ENST00000676320.1	c.1685-3dupT		splice_region_variant, intron_variant			NM_001352027.3	ENSP00000502222.1

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1274 AN: 108302 Hom.: 20 Cov.: 0

Gnomad AFR AF: 0.0393

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00398

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00618

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00424

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.0104

GnomAD3 exomes AF: 0.0132 AC: 637 AN: 48272 Hom.: 1 AF XY: 0.0126 AC XY: 321 AN XY: 25422

Gnomad AFR exome AF: 0.0282

Gnomad AMR exome AF: 0.0128

Gnomad ASJ exome AF: 0.0101

Gnomad EAS exome AF: 0.0139

Gnomad SAS exome AF: 0.0137

Gnomad FIN exome AF: 0.00244

Gnomad NFE exome AF: 0.0106

Gnomad OTH exome AF: 0.0167

GnomAD4 exome AF: 0.00944 AC: 3896 AN: 412924 Hom.: 0 Cov.: 0 AF XY: 0.00950 AC XY: 2072 AN XY: 218126

Gnomad4 AFR exome AF: 0.0281

Gnomad4 AMR exome AF: 0.00892

Gnomad4 ASJ exome AF: 0.00795

Gnomad4 EAS exome AF: 0.00699

Gnomad4 SAS exome AF: 0.0160

Gnomad4 FIN exome AF: 0.00537

Gnomad4 NFE exome AF: 0.00843

Gnomad4 OTH exome AF: 0.00996

GnomAD4 genome AF: 0.0118 AC: 1274 AN: 108314 Hom.: 20 Cov.: 0 AF XY: 0.0118 AC XY: 594 AN XY: 50164

Gnomad4 AFR AF: 0.0392

Gnomad4 AMR AF: 0.00397

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00141

Gnomad4 OTH AF: 0.0104

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs35995547; hg19: chr11-45957292;