11-45935741-TAAAAAAAAAAAAAA-T

Position:

• chr11-45935741-TAAAAAAAAAAAAAA-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001352027.3(PHF21A):​c.1685-16_1685-3delTTTTTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 523,662 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: PHF21A NM_001352027.3 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.62

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 11-45935741-TAAAAAAAAAAAAAA-T is Benign according to our data. Variant chr11-45935741-TAAAAAAAAAAAAAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 2703475.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 40 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF21A	NM_001352027.3	c.1685-16_1685-3delTTTTTTTTTTTTTT		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.1685-16_1685-3delTTTTTTTTTTTTTT		splice_region_variant, intron_variant			NM_001352027.3	ENSP00000502222.1

Frequencies

GnomAD3 genomes AF: 0.000323 AC: 35 AN: 108338 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000969

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000313 AC: 13 AN: 415310 Hom.: 0 AF XY: 0.0000365 AC XY: 8 AN XY: 219404

Gnomad4 AFR exome AF: 0.000564

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000252

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000154

Gnomad4 OTH exome AF: 0.0000925

GnomAD4 genome AF: 0.000369 AC: 40 AN: 108352 Hom.: 0 Cov.: 0 AF XY: 0.000379 AC XY: 19 AN XY: 50180

Gnomad4 AFR AF: 0.00136

Gnomad4 AMR AF: 0.0000968

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

PHF21A-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 09, 2019

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

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 18, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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;