rs1052532

chr15-90931006-T-Cchr15-90931006-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286451.2(HDDC3):c.*269A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 432,316 control chromosomes in the GnomAD database, including 19,312 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (6424 hom., cov: 32)
  • Exomes 𝑓: 0.29 (12888 hom.)
• Consequence: HDDC3 NM_001286451.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

Genes affected

HDDC3 (HGNC:30522): (HD domain containing 3) Predicted to enable guanosine-3',5'-bis(diphosphate) 3'-diphosphatase activity. [provided by Alliance of Genome Resources, Apr 2022]

UNC45A (HGNC:30594): (unc-45 myosin chaperone A) This gene encodes a regulatory component of the progesterone receptor/heat shock protein 90 chaperoning complex, which functions in the assembly and folding of the progesterone receptor. The encoded protein is thought to be essential for normal cell proliferation, and for the accumulation of myosin during development of muscle cells. [provided by RefSeq, Sep 2018]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDDC3	NM_001286451.2	c.*269A>G		3_prime_UTR_variant	4/4	ENST00000394272.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDDC3	ENST00000394272.8	c.*269A>G		3_prime_UTR_variant	4/4	2	NM_001286451.2	P1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42662 AN: 151928 Hom.: 6421 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.303

GnomAD4 exome AF: 0.289 AC: 80873 AN: 280270 Hom.: 12888 Cov.: 3 AF XY: 0.287 AC XY: 42517 AN XY: 148228

Gnomad4 AFR exome AF: 0.215

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.562

Gnomad4 SAS exome AF: 0.259

Gnomad4 FIN exome AF: 0.270

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.293

GnomAD4 genome AF: 0.281 AC: 42686 AN: 152046 Hom.: 6424 Cov.: 32 AF XY: 0.285 AC XY: 21143 AN XY: 74312

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.305

Alfa AF: 0.274 Hom.: 6404

Bravo AF: 0.288

Asia WGS AF: 0.443 AC: 1535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.5
Dann	Benign	0.58

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

Other links and lift over

dbSNP: rs1052532; hg19: chr15-91474236;