12-47789283-C-A

Variant names:

• chr12-47789283-C-A
• rs1211742793
• NM_015401.5:c.2213G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015401.5(HDAC7):​c.2213G>T​(p.Ser738Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S738R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HDAC7 NM_015401.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• Publications: 0 publications found

Genes affected

HDAC7 (HGNC:14067): (histone deacetylase 7) 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 has sequence homology to members of the histone deacetylase family. This gene is orthologous to mouse HDAC7 gene whose protein promotes repression mediated via the transcriptional corepressor SMRT. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39981577).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015401.5. 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
	HDAC7	NM_015401.5	MANE Select	c.2213G>T	p.Ser738Ile	missense	Exon 19 of 26	NP_056216.2	Q8WUI4-5
	HDAC7	NM_001368046.1		c.2255G>T	p.Ser752Ile	missense	Exon 19 of 26	NP_001354975.1
	HDAC7	NM_001308090.2		c.2162G>T	p.Ser721Ile	missense	Exon 18 of 25	NP_001295019.1	Q8WUI4-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC7	ENST00000080059.12	TSL:1 MANE Select	c.2213G>T	p.Ser738Ile	missense	Exon 19 of 26	ENSP00000080059.7	Q8WUI4-5
	HDAC7	ENST00000380610.8	TSL:2	c.2264G>T	p.Ser755Ile	missense	Exon 19 of 27	ENSP00000369984.4	J3KPH8
	HDAC7	ENST00000354334.7	TSL:1	c.2102G>T	p.Ser701Ile	missense	Exon 18 of 25	ENSP00000351326.3	Q8WUI4-7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461684 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727172

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111904

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	0.0090	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.63	D
Eigen	Benign	0.16
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.8
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.028	D
Sift4G	Benign	0.13	T
Polyphen		0.89	P
Vest4		0.42
MutPred		0.47		Loss of disorder (P = 0.0112)
MVP		0.36
MPC		1.8
ClinPred		0.98	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.65
gMVP		0.88
Mutation Taster		=57/43	polymorphism

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

Other links and lift over

dbSNP: rs1211742793; hg19: chr12-48183066;