Genetic Variant NM_001304509.2:c.46G>A (chr9-113374309-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001304509.2(HDHD3):c.46G>A(p.Asp16Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000255 in 1,530,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

HDHD3
NM_001304509.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.39

Publications

0 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: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34505457).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HDHD3	NM_001304509.2	MANE Select	c.46G>A	p.Asp16Asn	missense	Exon 3 of 3	NP_001291438.1	Q9BSH5
HDHD3	NM_001304510.2		c.46G>A	p.Asp16Asn	missense	Exon 3 of 3	NP_001291439.1	Q9BSH5
HDHD3	NM_001304511.2		c.46G>A	p.Asp16Asn	missense	Exon 2 of 2	NP_001291440.1	Q9BSH5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HDHD3	ENST00000374180.4	TSL:1 MANE Select	c.46G>A	p.Asp16Asn	missense	Exon 3 of 3	ENSP00000363295.3	Q9BSH5
HDHD3	ENST00000238379.9	TSL:1	c.46G>A	p.Asp16Asn	missense	Exon 2 of 2	ENSP00000238379.5	Q9BSH5
HDHD3	ENST00000900262.1		c.46G>A	p.Asp16Asn	missense	Exon 4 of 4	ENSP00000570321.1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000267

AC:

AN:

187546

AF XY:

0.0000201

show subpopulations

Gnomad AFR exome

AF:

0.000327

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000131

AC:

AN:

1378574

Hom.:

Cov.:

AF XY:

0.00000887

AC XY:

AN XY:

676420

show subpopulations

African (AFR)

AF:

0.000455

AC:

AN:

30798

American (AMR)

AF:

0.0000628

AC:

AN:

31842

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20800

East Asian (EAS)

AF:

0.00

AC:

AN:

38770

South Asian (SAS)

AF:

0.00

AC:

AN:

74402

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5314

European-Non Finnish (NFE)

AF:

9.35e-7

AC:

AN:

1069626

Other (OTH)

AF:

0.0000176

AC:

AN:

56674

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000138

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.000457

AC:

AN:

41582

American (AMR)

AF:

0.000131

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000219

Hom.:

Bravo

AF:

0.000132

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000248

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.76

M_CAP

Benign

0.014

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.4

PhyloP100

5.4

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.2

REVEL

Benign

0.23

Sift

Benign

0.35

Sift4G

Benign

0.26

Polyphen

1.0

Vest4

0.50

MVP

0.60

MPC

0.14

ClinPred

0.17

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.27

gMVP

0.94

Mutation Taster

=9/91

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over