chr11-45935741-TAAA-T

Position:

• chr11-45935741-TAAA-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_001352027.3(PHF21A):​c.1685-5_1685-3delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0927 in 504,642 control chromosomes in the GnomAD database, including 3 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00042 (0 hom., cov: 0)
  • Exomes 𝑓: 0.12 (3 hom.)
• Consequence: PHF21A NM_001352027.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

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 -9 ACMG points.

• BP6: Variant 11-45935741-TAAA-T is Benign according to our data. Variant chr11-45935741-TAAA-T is described in Lovd as [Likely_benign].
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF21A	NM_001352027.3	c.1685-5_1685-3delTTT		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.1685-5_1685-3delTTT		splice_region_variant, intron_variant			NM_001352027.3	ENSP00000502222.1

Frequencies

GnomAD3 genomes AF: 0.000415 AC: 45 AN: 108320 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000350

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000291

Gnomad ASJ AF: 0.00241

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00197

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000335

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0849 AC: 4097 AN: 48272 Hom.: 0 AF XY: 0.0829 AC XY: 2108 AN XY: 25422

Gnomad AFR exome AF: 0.0692

Gnomad AMR exome AF: 0.133

Gnomad ASJ exome AF: 0.0790

Gnomad EAS exome AF: 0.108

Gnomad SAS exome AF: 0.0774

Gnomad FIN exome AF: 0.0371

Gnomad NFE exome AF: 0.0736

Gnomad OTH exome AF: 0.0981

GnomAD4 exome AF: 0.118 AC: 46754 AN: 396308 Hom.: 3 AF XY: 0.116 AC XY: 24357 AN XY: 209432

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.120

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.120

Gnomad4 SAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.000415 AC: 45 AN: 108334 Hom.: 0 Cov.: 0 AF XY: 0.000498 AC XY: 25 AN XY: 50172

Gnomad4 AFR AF: 0.000349

Gnomad4 AMR AF: 0.000291

Gnomad4 ASJ AF: 0.00241

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00197

Gnomad4 NFE AF: 0.000335

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs35995547; hg19: chr11-45957292;