rs10501316

Variant names:

• chr11-46068999-C-T
• rs10501316
• NM_001352027.3:c.153+7755G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352027.3(PHF21A):​c.153+7755G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,104 control chromosomes in the GnomAD database, including 1,643 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1643 hom., cov: 32)
• Consequence: PHF21A NM_001352027.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.808
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• Potocki-Shaffer syndrome

  Inheritance: AD Classification: STRONG Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352027.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF21A	NM_001352027.3	MANE Select	c.153+7755G>A		intron	N/A	NP_001338956.1	Q96BD5-3
	PHF21A	NM_001441167.1		c.174+7755G>A		intron	N/A	NP_001428096.1
	PHF21A	NM_001441168.1		c.174+7755G>A		intron	N/A	NP_001428097.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF21A	ENST00000676320.1	MANE Select	c.153+7755G>A		intron	N/A	ENSP00000502222.1	Q96BD5-3
	PHF21A	ENST00000323180.10	TSL:1	c.153+7755G>A		intron	N/A	ENSP00000323152.6	Q96BD5-2
	PHF21A	ENST00000863274.1		c.174+7755G>A		intron	N/A	ENSP00000533333.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21048 AN: 151986 Hom.: 1644 Cov.: 32

Gnomad AFR AF: 0.0891

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0992

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.120

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.138 AC: 21059 AN: 152104 Hom.: 1643 Cov.: 32 AF XY: 0.139 AC XY: 10301 AN XY: 74354

African (AFR) AF: 0.0893 AC: 3708 AN: 41502

American (AMR) AF: 0.102 AC: 1567 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0992 AC: 344 AN: 3468

East Asian (EAS) AF: 0.150 AC: 776 AN: 5176

South Asian (SAS) AF: 0.136 AC: 657 AN: 4826

European-Finnish (FIN) AF: 0.199 AC: 2099 AN: 10566

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11467 AN: 67960

Other (OTH) AF: 0.119 AC: 252 AN: 2110

Alfa AF: 0.155 Hom.: 3535

Bravo AF: 0.129

Asia WGS AF: 0.136 AC: 472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.52
DANN	Benign	0.45
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10501316;

hg19: chr11-46090550;