Genetic Variant PHF21A:c.1685-15_1685-3delTTTTTTTTTTTTT (chr11-45935741-TAAAAAAAAAAAAA-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001352027.3(PHF21A):c.1685-15_1685-3delTTTTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000802 in 523,646 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000083 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

PHF21A
NM_001352027.3 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.62

Publications

2 publications found

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 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Potocki-Shaffer syndrome
Inheritance: AD Classification: STRONG Submitted by: G2P

PHF21A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 11-45935741-TAAAAAAAAAAAAA-T is Benign according to our data. Variant chr11-45935741-TAAAAAAAAAAAAA-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1979745.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF21A	NM_001352027.3 link	c.1685-15_1685-3delTTTTTTTTTTTTT		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 link	c.1685-15_1685-3delTTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 17 of 18		NM_001352027.3	ENSP00000502222.1		Q96BD5-3

Frequencies

GnomAD3 genomes

AF:

0.0000831

AC:

AN:

108338

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000291

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:

0.0000372

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000795

AC:

AN:

415308

Hom.:

AF XY:

0.0000547

AC XY:

AN XY:

219404

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

10636

American (AMR)

AF:

0.0000591

AC:

AN:

16922

Ashkenazi Jewish (ASJ)

AF:

0.0000833

AC:

AN:

12008

East Asian (EAS)

AF:

0.00

AC:

AN:

25896

South Asian (SAS)

AF:

0.00

AC:

AN:

39626

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26210

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2206

European-Non Finnish (NFE)

AF:

0.000115

AC:

AN:

260194

Other (OTH)

AF:

0.0000463

AC:

AN:

21610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.649

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000831

AC:

AN:

108338

Hom.:

Cov.:

AF XY:

0.0000997

AC XY:

AN XY:

50148

show subpopulations

African (AFR)

AF:

0.000140

AC:

AN:

28564

American (AMR)

AF:

0.000291

AC:

AN:

10320

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2910

East Asian (EAS)

AF:

0.00

AC:

AN:

3728

South Asian (SAS)

AF:

0.00

AC:

AN:

3076

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0000372

AC:

AN:

53784

Other (OTH)

AF:

0.00

AC:

AN:

1436

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.619

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 05, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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11-45935741-TAAAAAAAAAAAAAA-TA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over