11-45934077-T-C

Position:

chr11-45934077-T-C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2

The NM_001352027.3(PHF21A):c.1937A>G(p.Asn646Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00047 in 1,613,976 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 16 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 7 hom. )

Consequence

PHF21A
NM_001352027.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.66

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PHF21A. . Gene score misZ 2.8609 (greater than the threshold 3.09). Trascript score misZ 3.1268 (greater than threshold 3.09). GenCC has associacion of gene with complex neurodevelopmental disorder, intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures, Potocki-Shaffer syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.007928789).

BP6

Variant 11-45934077-T-C is Benign according to our data. Variant chr11-45934077-T-C is described in ClinVar as [Benign]. Clinvar id is 1618357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00276 (420/152182) while in subpopulation AMR AF= 0.0268 (410/15278). AF 95% confidence interval is 0.0247. There are 16 homozygotes in gnomad4. There are 293 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 420 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHF21A	NM_001352027.3 linkuse as main transcript	c.1937A>G	p.Asn646Ser	missense_variant	19/19	ENST00000676320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHF21A	ENST00000676320.1 linkuse as main transcript	c.1937A>G	p.Asn646Ser	missense_variant	19/19		NM_001352027.3	P3	Q96BD5-3

Frequencies

GnomAD3 genomes

AF:

0.00276

AC:

420

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0269

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000894

AC:

224

AN:

250564

Hom.:

AF XY:

0.000922

AC XY:

125

AN XY:

135566

show subpopulations

Gnomad AFR exome

AF:

0.0000621

Gnomad AMR exome

AF:

0.00614

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000442

Gnomad OTH exome

AF:

0.000655

GnomAD4 exome

AF:

0.000232

AC:

339

AN:

1461794

Hom.:

Cov.:

AF XY:

0.000245

AC XY:

178

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.00635

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.00276

AC:

420

AN:

152182

Hom.:

Cov.:

AF XY:

0.00394

AC XY:

293

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.0268

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000133

Hom.:

Bravo

AF:

0.00260

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

PHF21A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 01, 2021

This variant is classified as 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

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.058

.;T;T

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.027

MetaRNN

Benign

0.0079

T;T;T

MetaSVM

Uncertain

0.17

MutationAssessor

Benign

1.1

.;L;.

MutationTaster

Benign

0.86

D;D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.030

N;N;N

REVEL

Benign

0.25

Sift

Uncertain

0.013

D;D;T

Sift4G

Benign

0.56

T;T;.

Polyphen

0.74

P;P;.

Vest4

0.31

MVP

0.62

MPC

0.16

ClinPred

0.068

GERP RS

5.8

Varity_R

0.12

gMVP

0.34

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over