rs3750526

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000374180.4(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
ENST00000374180.4 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00900
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
HDHD3NM_001304509.2 linkuse as main transcriptc.-446C>G 5_prime_UTR_variant 1/3 ENST00000374180.4 NP_001291438.1
HDHD3NM_001304510.2 linkuse as main transcriptc.-405C>G 5_prime_UTR_variant 1/3 NP_001291439.1
HDHD3NM_001304511.2 linkuse as main transcriptc.-331C>G 5_prime_UTR_variant 1/2 NP_001291440.1
HDHD3NM_001371923.1 linkuse as main transcriptc.-291+42C>G intron_variant NP_001358852.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HDHD3ENST00000374180.4 linkuse as main transcriptc.-446C>G 5_prime_UTR_variant 1/31 NM_001304509.2 ENSP00000363295 P1
HDHD3ENST00000485934.1 linkuse as main transcriptn.42C>G non_coding_transcript_exon_variant 1/32

Frequencies

GnomAD3 genomes
AF:
0.109
AC:
16584
AN:
152048
Hom.:
1274
Cov.:
32
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:
5
AN:
74
Hom.:
0
Cov.:
0
AF XY:
0.0806
AC XY:
5
AN XY:
62
show subpopulations
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
show subpopulations
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3750526; hg19: chr9-116139164; API