dbSNP rs3750526: HDHD3:c.-446C>G (chr9-113376884-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00900

Publications

1 publications found

Variant links:

Genes affected

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

HDHD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
HDHD3	NM_001304509.2 link	c.-446C>G	5_prime_UTR_variant	Exon 1 of 3	ENST00000374180.4	NP_001291438.1
HDHD3	NM_001304510.2 link	c.-405C>G	5_prime_UTR_variant	Exon 1 of 3		NP_001291439.1
HDHD3	NM_001304511.2 link	c.-331C>G	5_prime_UTR_variant	Exon 1 of 2		NP_001291440.1
HDHD3	NM_001371923.1 link	c.-291+42C>G	intron_variant	Intron 1 of 2		NP_001358852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDHD3	ENST00000374180.4 link	c.-446C>G		5_prime_UTR_variant	Exon 1 of 3	1	NM_001304509.2	ENSP00000363295.3
HDHD3	ENST00000485934.1 link	n.42C>G		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16584

AN:

152048

Hom.:

1274

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.0806

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0667

AC:

AN:

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.109

AC:

16602

AN:

152164

Hom.:

1274

Cov.:

AF XY:

0.109

AC XY:

8108

AN XY:

74408

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0650

AC:

4419

AN:

67978

Other (OTH)

AF:

0.0942

AC:

199

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

675

1350

2024

2699

3374

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.64

PhyloP100

0.0090

PromoterAI

-0.0086

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over