rs1052532

Variant names:

• chr15-90931006-T-C
• rs1052532
• NM_001286451.2:c.*269A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-90931006-T-C
• chr15-90931006-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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]

UNC45A Gene-Disease associations (from GenCC):

• osteootohepatoenteric syndrome

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286451.2. 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
	HDDC3	NM_001286451.2	MANE Select	c.*269A>G		3_prime_UTR	Exon 4 of 4	NP_001273380.1	Q8N4P3-1
	HDDC3	NM_198527.4		c.*537A>G		3_prime_UTR	Exon 4 of 4	NP_940929.1	Q8N4P3-2
	UNC45A	NM_001039675.2		c.-760+751T>C		intron	N/A	NP_001034764.1	Q9H3U1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDDC3	ENST00000394272.8	TSL:2 MANE Select	c.*269A>G		3_prime_UTR	Exon 4 of 4	ENSP00000377814.4	Q8N4P3-1
	HDDC3	ENST00000330334.7	TSL:1	c.*537A>G		3_prime_UTR	Exon 4 of 4	ENSP00000330721.3	Q8N4P3-2
	UNC45A	ENST00000480470.5	TSL:4	c.-111T>C		5_prime_UTR	Exon 2 of 5	ENSP00000500895.1	A0A5F9ZI32

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

African (AFR) AF: 0.215 AC: 1954 AN: 9078

American (AMR) AF: 0.355 AC: 4063 AN: 11448

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 2028 AN: 8568

East Asian (EAS) AF: 0.562 AC: 9430 AN: 16792

South Asian (SAS) AF: 0.259 AC: 8658 AN: 33440

European-Finnish (FIN) AF: 0.270 AC: 4223 AN: 15654

Middle Eastern (MID) AF: 0.286 AC: 339 AN: 1186

European-Non Finnish (NFE) AF: 0.271 AC: 45421 AN: 167882

Other (OTH) AF: 0.293 AC: 4757 AN: 16222

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

African (AFR) AF: 0.220 AC: 9113 AN: 41460

American (AMR) AF: 0.354 AC: 5400 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 804 AN: 3470

East Asian (EAS) AF: 0.572 AC: 2958 AN: 5172

South Asian (SAS) AF: 0.265 AC: 1275 AN: 4816

European-Finnish (FIN) AF: 0.291 AC: 3077 AN: 10568

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19083 AN: 67972

Other (OTH) AF: 0.305 AC: 645 AN: 2112

Alfa AF: 0.276 Hom.: 9329

Bravo AF: 0.288

Asia WGS AF: 0.443 AC: 1535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.5
DANN	Benign	0.58
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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: rs1052532; hg19: chr15-91474236;