9-113374258-C-T

Variant summary

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

The NM_001304509.2(HDHD3):​c.97G>A​(p.Ala33Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000163 in 1,598,700 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

HDHD3
NM_001304509.2 missense

Scores

6
5
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.09
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.97G>A p.Ala33Thr 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.97G>A p.Ala33Thr missense_variant Exon 3 of 3 1 NM_001304509.2 ENSP00000363295.3 Q9BSH5
HDHD3ENST00000238379.9 linkc.97G>A p.Ala33Thr missense_variant Exon 2 of 2 1 ENSP00000238379.5 Q9BSH5
HDHD3ENST00000485934.1 linkn.543G>A non_coding_transcript_exon_variant Exon 3 of 3 2

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152204
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000837
AC:
20
AN:
238948
Hom.:
0
AF XY:
0.0000696
AC XY:
9
AN XY:
129252
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000308
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000148
Gnomad OTH exome
AF:
0.000519
GnomAD4 exome
AF:
0.000173
AC:
250
AN:
1446496
Hom.:
0
Cov.:
33
AF XY:
0.000169
AC XY:
121
AN XY:
717634
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000212
Gnomad4 OTH exome
AF:
0.000269
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152204
Hom.:
0
Cov.:
33
AF XY:
0.0000941
AC XY:
7
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000111
Hom.:
0
Bravo
AF:
0.0000793
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000330
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 20, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.97G>A (p.A33T) 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 97, causing the alanine (A) at amino acid position 33 to be replaced by a threonine (T). 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
Pathogenic
0.64
BayesDel_addAF
Benign
-0.074
T
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.19
T;T
Eigen
Pathogenic
0.81
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.78
.;T
M_CAP
Benign
0.028
D
MetaRNN
Uncertain
0.71
D;D
MetaSVM
Benign
-0.38
T
MutationAssessor
Pathogenic
3.5
H;H
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-3.4
D;D
REVEL
Uncertain
0.37
Sift
Uncertain
0.0040
D;D
Sift4G
Benign
0.074
T;T
Polyphen
0.99
D;D
Vest4
0.54
MVP
0.78
MPC
0.58
ClinPred
0.95
D
GERP RS
6.0
Varity_R
0.62
gMVP
0.88

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: rs375470765; hg19: chr9-116136538; API