rs987884779

Variant names:

• chr12-47791299-G-A
• rs987884779
• NM_015401.5:c.1943C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-47791299-G-A
• chr12-47791299-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015401.5(HDAC7):​c.1943C>T​(p.Ala648Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000208 in 1,445,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. A648G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: HDAC7 NM_015401.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.53
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18803757).

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.1943C>T	p.Ala648Val	missense	Exon 16 of 26	NP_056216.2	Q8WUI4-5
	HDAC7	NM_001368046.1		c.1985C>T	p.Ala662Val	missense	Exon 16 of 26	NP_001354975.1
	HDAC7	NM_001308090.2		c.1892C>T	p.Ala631Val	missense	Exon 15 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.1943C>T	p.Ala648Val	missense	Exon 16 of 26	ENSP00000080059.7	Q8WUI4-5
	HDAC7	ENST00000380610.8	TSL:2	c.1994C>T	p.Ala665Val	missense	Exon 16 of 27	ENSP00000369984.4	J3KPH8
	HDAC7	ENST00000354334.7	TSL:1	c.1832C>T	p.Ala611Val	missense	Exon 15 of 25	ENSP00000351326.3	Q8WUI4-7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1445366 Hom.: 0 Cov.: 31 AF XY: 0.00000279 AC XY: 2 AN XY: 717590

African (AFR) AF: 0.00 AC: 0 AN: 32926

American (AMR) AF: 0.00 AC: 0 AN: 42870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25644

East Asian (EAS) AF: 0.00 AC: 0 AN: 38706

South Asian (SAS) AF: 0.00 AC: 0 AN: 83476

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00000272 AC: 3 AN: 1104096

Other (OTH) AF: 0.00 AC: 0 AN: 59660

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	0.032
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.29	N
PhyloP100		4.5
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.064
Sift	Benign	0.56	T
Sift4G	Benign	0.77	T
Polyphen		0.0080	B
Vest4		0.41
MutPred		0.54		Gain of catalytic residue at A644 (P = 0.0204)
MVP		0.40
MPC		0.32
ClinPred		0.53	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.28
gMVP		0.63
Mutation Taster		=36/64	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs987884779; hg19: chr12-48185082;