rs1943124292

Variant names:

• chr12-47785465-G-A
• rs1943124292
• NM_015401.5:c.2713C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-47785465-G-A
• chr12-47785465-G-C
• chr12-47785465-G-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.2713C>T​(p.Pro905Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: HDAC7 NM_015401.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.42
• 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]

ENSG00000268069 (HGNC:):

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=0.35569346).

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.2713C>T	p.Pro905Ser	missense	Exon 24 of 26	NP_056216.2	Q8WUI4-5
	HDAC7	NM_001368046.1		c.2755C>T	p.Pro919Ser	missense	Exon 24 of 26	NP_001354975.1
	HDAC7	NM_001308090.2		c.2662C>T	p.Pro888Ser	missense	Exon 23 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.2713C>T	p.Pro905Ser	missense	Exon 24 of 26	ENSP00000080059.7	Q8WUI4-5
	HDAC7	ENST00000380610.8	TSL:2	c.2764C>T	p.Pro922Ser	missense	Exon 24 of 27	ENSP00000369984.4	J3KPH8
	HDAC7	ENST00000354334.7	TSL:1	c.2602C>T	p.Pro868Ser	missense	Exon 23 of 25	ENSP00000351326.3	Q8WUI4-7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1459940 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726242

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

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44400

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25976

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 85952

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111090

Other (OTH) AF: 0.0000166 AC: 1 AN: 60296

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000192981), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000314 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D
Eigen	Benign	0.19
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		7.4
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.012	D
Sift4G	Benign	0.099	T
Polyphen		0.0040	B
Vest4		0.39
MutPred		0.45		Gain of catalytic residue at N901 (P = 0.0129)
MVP		0.76
MPC		1.4
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.87
gMVP		0.77
Mutation Taster		=41/59	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs1943124292; hg19: chr12-48179248;