dbSNP rs35702540: HDHD5:p.Val232Ile (chr22-17141111-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_033070.3(HDHD5):c.694G>A(p.Val232Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00194 in 1,594,554 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0099 ( 23 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 18 hom. )

Consequence

HDHD5
NM_033070.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.370

Publications

5 publications found

Variant links:

Genes affected

HDHD5 (HGNC:1843): (haloacid dehalogenase like hydrolase domain containing 5) Predicted to be involved in glycerophospholipid biosynthetic process. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

HDHD5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007979363).

BP6

Variant 22-17141111-C-T is Benign according to our data. Variant chr22-17141111-C-T is described in ClinVar as Benign. ClinVar VariationId is 711763.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00992 (1511/152254) while in subpopulation AFR AF = 0.0334 (1389/41558). AF 95% confidence interval is 0.032. There are 23 homozygotes in GnomAd4. There are 721 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033070.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDHD5	NM_033070.3	MANE Select	c.694G>A	p.Val232Ile	missense	Exon 6 of 8	NP_149061.1	Q9BXW7-1
	HDHD5	NM_017829.6		c.604G>A	p.Val202Ile	missense	Exon 6 of 8	NP_060299.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HDHD5	ENST00000336737.8	TSL:1 MANE Select	c.694G>A	p.Val232Ile	missense	Exon 6 of 8	ENSP00000337358.4	Q9BXW7-1
HDHD5	ENST00000155674.9	TSL:1	c.604G>A	p.Val202Ile	missense	Exon 6 of 8	ENSP00000155674.5	Q9BXW7-2
HDHD5	ENST00000477157.5	TSL:1	n.2537G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.00991

AC:

1507

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0334

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00622

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00719

GnomAD2 exomes

AF:

0.00267

AC:

615

AN:

230728

AF XY:

0.00193

show subpopulations

Gnomad AFR exome

AF:

0.0366

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000161

Gnomad OTH exome

AF:

0.00129

GnomAD4 exome

AF:

0.00109

AC:

1578

AN:

1442300

Hom.:

Cov.:

AF XY:

0.000961

AC XY:

689

AN XY:

717312

show subpopulations

African (AFR)

AF:

0.0369

AC:

1177

AN:

31920

American (AMR)

AF:

0.00225

AC:

AN:

41356

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25426

East Asian (EAS)

AF:

0.0000267

AC:

AN:

37498

South Asian (SAS)

AF:

0.0000597

AC:

AN:

83724

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53256

Middle Eastern (MID)

AF:

0.000704

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

0.000164

AC:

181

AN:

1103878

Other (OTH)

AF:

0.00196

AC:

117

AN:

59560

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

160

240

320

400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.00992

AC:

1511

AN:

152254

Hom.:

Cov.:

AF XY:

0.00969

AC XY:

721

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0334

AC:

1389

AN:

41558

American (AMR)

AF:

0.00621

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.000414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68002

Other (OTH)

AF:

0.00712

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

158

237

316

395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00378

Hom.:

Bravo

AF:

0.0120

ESP6500AA

AF:

0.0354

AC:

156

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00331

AC:

402

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.9

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.0069

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0080

MetaSVM

Benign

-1.0

PhyloP100

0.37

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.34

REVEL

Benign

0.068

Sift

Benign

0.23

Sift4G

Benign

0.24

Polyphen

0.18

Vest4

0.27

MVP

0.040

MPC

0.17

ClinPred

0.0096

GERP RS

3.0

Varity_R

0.024

gMVP

0.46

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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