chr9-113376884-G-C

Variant names:

• chr9-113376884-G-C
• rs3750526
• NM_001304509.2:c.-446C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304509.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDHD3	NM_001304509.2	MANE Select	c.-446C>G		5_prime_UTR	Exon 1 of 3	NP_001291438.1
	HDHD3	NM_001304510.2		c.-405C>G		5_prime_UTR	Exon 1 of 3	NP_001291439.1
	HDHD3	NM_001304511.2		c.-331C>G		5_prime_UTR	Exon 1 of 2	NP_001291440.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDHD3	ENST00000374180.4	TSL:1 MANE Select	c.-446C>G		5_prime_UTR	Exon 1 of 3	ENSP00000363295.3
	HDHD3	ENST00000485934.1	TSL:2	n.42C>G		non_coding_transcript_exon	Exon 1 of 3

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

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0667 AC: 4 AN: 60

Other (OTH) AF: 0.167 AC: 1 AN: 6

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

African (AFR) AF: 0.197 AC: 8173 AN: 41530

American (AMR) AF: 0.0827 AC: 1266 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0530 AC: 184 AN: 3472

East Asian (EAS) AF: 0.241 AC: 1233 AN: 5118

South Asian (SAS) AF: 0.0680 AC: 328 AN: 4822

European-Finnish (FIN) AF: 0.0691 AC: 734 AN: 10622

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0650 AC: 4419 AN: 67978

Other (OTH) AF: 0.0942 AC: 199 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.1
DANN	Benign	0.64
PhyloP100		0.0090
PromoterAI		-0.0086	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3750526; hg19: chr9-116139164;