9-113373850-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001304509.2(HDHD3):​c.505G>A​(p.Asp169Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HDHD3
NM_001304509.2 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.38
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HDHD3NM_001304509.2 linkc.505G>A p.Asp169Asn missense_variant Exon 3 of 3 ENST00000374180.4 NP_001291438.1 Q9BSH5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HDHD3ENST00000374180.4 linkc.505G>A p.Asp169Asn missense_variant Exon 3 of 3 1 NM_001304509.2 ENSP00000363295.3 Q9BSH5
HDHD3ENST00000238379.9 linkc.505G>A p.Asp169Asn missense_variant Exon 2 of 2 1 ENSP00000238379.5 Q9BSH5
HDHD3ENST00000485934.1 linkn.*38G>A downstream_gene_variant 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251264
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135810
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461838
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 29, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.505G>A (p.D169N) alteration is located in exon 2 (coding exon 1) of the HDHD3 gene. This alteration results from a G to A substitution at nucleotide position 505, causing the aspartic acid (D) at amino acid position 169 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T;T
Eigen
Uncertain
0.24
Eigen_PC
Benign
0.22
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.93
.;D
M_CAP
Benign
0.016
T
MetaRNN
Uncertain
0.43
T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Uncertain
2.1
M;M
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-2.0
N;N
REVEL
Benign
0.23
Sift
Benign
0.10
T;T
Sift4G
Benign
0.21
T;T
Polyphen
0.96
D;D
Vest4
0.28
MutPred
0.62
Loss of ubiquitination at K167 (P = 0.0672);Loss of ubiquitination at K167 (P = 0.0672);
MVP
0.67
MPC
0.42
ClinPred
0.79
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.40
gMVP
0.46

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs769600567; hg19: chr9-116136130; API