Variant rs115552422 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001378414.1(HDAC4):c.3220G>C(p.Ala1074Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HDAC4
NM_001378414.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.999

Variant links:

Genes affected

HDAC4 (HGNC:14063): (histone deacetylase 4) Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class II of the histone deacetylase/acuc/apha family. It possesses histone deacetylase activity and represses transcription when tethered to a promoter. This protein does not bind DNA directly, but through transcription factors MEF2C and MEF2D. It seems to interact in a multiprotein complex with RbAp48 and HDAC3. [provided by RefSeq, Jul 2008]

HDAC4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09843698).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC4	NM_001378414.1 link	c.3220G>C	p.Ala1074Pro	missense_variant	Exon 26 of 27	ENST00000543185.6	NP_001365343.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HDAC4	ENST00000543185.6 link	c.3220G>C	p.Ala1074Pro	missense_variant	Exon 26 of 27	5	NM_001378414.1	ENSP00000440481.3	A0A7I2SVS4
HDAC4	ENST00000345617.7 link	c.3205G>C	p.Ala1069Pro	missense_variant	Exon 26 of 27	1		ENSP00000264606.3	P56524-1
HDAC4	ENST00000430200.1 link	c.475G>C	p.Ala159Pro	missense_variant	Exon 3 of 4	3		ENSP00000410551.1	H7C397
HDAC4	ENST00000690129.1 link	n.1234G>C		non_coding_transcript_exon_variant	Exon 9 of 10

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249986

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135318

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460596

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726528

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.36

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.043

MetaRNN

Benign

0.098

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.92

L;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.4

N;.

REVEL

Benign

0.050

Sift

Benign

0.23

T;.

Sift4G

Benign

0.27

T;T

Polyphen

0.0

B;.

Vest4

0.24

MutPred

0.18

Gain of catalytic residue at P1068 (P = 0.0133);.;

MVP

0.50

MPC

1.0

ClinPred

0.34

GERP RS

1.8

Varity_R

0.13

gMVP

0.30

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over