rs3750526

Positions:

• chr9-113376884-G-C

Variant summary

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

The NM_001304509.2(HDHD3):​c.-446C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,238 control chromosomes in the GnomAD database, including 1,274 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 0.11 (1274 hom., cov: 32)
  • Exomes 𝑓: 0.068 (0 hom.)
• Consequence: HDHD3 NM_001304509.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900

Genes affected

HDHD3 (HGNC:28171): (haloacid dehalogenase like hydrolase domain containing 3) Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

HDHD3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDHD3	NM_001304509.2	c.-446C>G		5_prime_UTR_variant	1/3	ENST00000374180.4	NP_001291438.1
HDHD3	NM_001304510.2	c.-405C>G		5_prime_UTR_variant	1/3		NP_001291439.1
HDHD3	NM_001304511.2	c.-331C>G		5_prime_UTR_variant	1/2		NP_001291440.1
HDHD3	NM_001371923.1	c.-291+42C>G		intron_variant			NP_001358852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDHD3	ENST00000374180.4	c.-446C>G		5_prime_UTR_variant	1/3	1	NM_001304509.2	ENSP00000363295.3
HDHD3	ENST00000485934.1	n.42C>G		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16584 AN: 152048 Hom.: 1274 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0829

Gnomad ASJ AF: 0.0530

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.0680

Gnomad FIN AF: 0.0691

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0651

Gnomad OTH AF: 0.0948

GnomAD4 exome AF: 0.0676 AC: 5 AN: 74 Hom.: 0 Cov.: 0 AF XY: 0.0806 AC XY: 5 AN XY: 62

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0667

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.109 AC: 16602 AN: 152164 Hom.: 1274 Cov.: 32 AF XY: 0.109 AC XY: 8108 AN XY: 74408

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.0827

Gnomad4 ASJ AF: 0.0530

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.0680

Gnomad4 FIN AF: 0.0691

Gnomad4 NFE AF: 0.0650

Gnomad4 OTH AF: 0.0942

Alfa AF: 0.0953 Hom.: 117

Bravo AF: 0.114

Asia WGS AF: 0.127 AC: 440 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.1
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3750526; hg19: chr9-116139164;