chr11-45935741-T-TAA

Variant names:

• chr11-45935741-T-TAA
• rs35995547
• NM_001352027.3:c.1685-4_1685-3dupTT

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_001352027.3(PHF21A):​c.1685-4_1685-3dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0015 (0 hom.)
• Consequence: PHF21A NM_001352027.3 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• 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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 11-45935741-T-TAA is Benign according to our data. Variant chr11-45935741-T-TAA is described in ClinVar as [Likely_benign]. Clinvar id is 3042619.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 292 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF21A	NM_001352027.3	c.1685-4_1685-3dupTT		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	c.1685-3_1685-2insTT		splice_region_variant, intron_variant	Intron 17 of 18		NM_001352027.3	ENSP00000502222.1

Frequencies

GnomAD3 genomes AF: 0.00270 AC: 293 AN: 108322 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00974

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00116

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: 0.00

Gnomad OTH AF: 0.00139

GnomAD4 exome AF: 0.00150 AC: 621 AN: 414452 Hom.: 0 Cov.: 0 AF XY: 0.00156 AC XY: 341 AN XY: 218948

Gnomad4 AFR exome AF: 0.00738

Gnomad4 AMR exome AF: 0.00142

Gnomad4 ASJ exome AF: 0.000918

Gnomad4 EAS exome AF: 0.00155

Gnomad4 SAS exome AF: 0.00284

Gnomad4 FIN exome AF: 0.000688

Gnomad4 NFE exome AF: 0.00114

Gnomad4 OTH exome AF: 0.00195

GnomAD4 genome AF: 0.00270 AC: 292 AN: 108332 Hom.: 1 Cov.: 0 AF XY: 0.00281 AC XY: 141 AN XY: 50174

Gnomad4 AFR AF: 0.00972

Gnomad4 AMR AF: 0.00107

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00139

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PHF21A-related disorder Benign:1

Oct 01, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

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;