Genetic Variant PHF21A:c.1685-7_1685-3dupTTTTT (chr11-45935741-T-TAAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001352027.3(PHF21A):c.1685-7_1685-3dupTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000037 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

PHF21A
NM_001352027.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF21A	NM_001352027.3 link	c.1685-7_1685-3dupTTTTT		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.1685-3_1685-2insTTTTT		splice_region_variant, intron_variant	Intron 17 of 18		NM_001352027.3	ENSP00000502222.1		Q96BD5-3

Frequencies

GnomAD3 genomes

AF:

0.0000369

AC:

AN:

108336

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000350

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000344

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:

0.0000289

AC:

AN:

415296

Hom.:

Cov.:

AF XY:

0.0000365

AC XY:

AN XY:

219392

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000282

AC:

AN:

10636

American (AMR)

AF:

0.00

AC:

AN:

16922

Ashkenazi Jewish (ASJ)

AF:

0.0000833

AC:

AN:

12008

East Asian (EAS)

AF:

0.00

AC:

AN:

25894

South Asian (SAS)

AF:

0.0000505

AC:

AN:

39624

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26210

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2206

European-Non Finnish (NFE)

AF:

0.0000231

AC:

AN:

260186

Other (OTH)

AF:

0.00

AC:

AN:

21610

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.292

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:

0.0000369

AC:

AN:

108336

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

50146

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000350

AC:

AN:

28564

American (AMR)

AF:

0.00

AC:

AN:

10320

Ashkenazi Jewish (ASJ)

AF:

0.000344

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:

53782

Other (OTH)

AF:

0.00

AC:

AN:

1436

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000197943), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.313

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Splicing

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

Publications

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11-45935741-TAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over