Genetic Variant HSDL2:p.Lys91Ile (chr9-112405714-A-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_032303.5(HSDL2):c.272A>T(p.Lys91Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,600,750 control chromosomes in the GnomAD database, including 140 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 21 hom., cov: 32)

Exomes 𝑓: 0.012 ( 119 hom. )

Consequence

HSDL2
NM_032303.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.977

Variant links:

Genes affected

HSDL2 (HGNC:18572): (hydroxysteroid dehydrogenase like 2) Predicted to enable oxidoreductase activity. Located in mitochondrion and peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

HSDL2 links:

HSDL2-AS1 (HGNC:31438): (HSDL2 antisense RNA 1)

HSDL2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010041714).

BP6

Variant 9-112405714-A-T is Benign according to our data. Variant chr9-112405714-A-T is described in ClinVar as [Benign]. Clinvar id is 770752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSDL2	NM_032303.5 link	c.272A>T	p.Lys91Ile	missense_variant	Exon 3 of 11	ENST00000398805.8	NP_115679.2	Q6YN16-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSDL2	ENST00000398805.8 link	c.272A>T	p.Lys91Ile	missense_variant	Exon 3 of 11	1	NM_032303.5	ENSP00000381785.3		Q6YN16-1

Frequencies

GnomAD3 genomes

AF:

0.00840

AC:

1279

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00220

Gnomad AMI

AF:

0.0779

Gnomad AMR

AF:

0.00681

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00856

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0132

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00836

AC:

2053

AN:

245578

Hom.:

AF XY:

0.00842

AC XY:

1121

AN XY:

133184

show subpopulations

Gnomad AFR exome

AF:

0.00195

Gnomad AMR exome

AF:

0.00347

Gnomad ASJ exome

AF:

0.00191

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00355

Gnomad FIN exome

AF:

0.00855

Gnomad NFE exome

AF:

0.0138

Gnomad OTH exome

AF:

0.00821

GnomAD4 exome

AF:

0.0117

AC:

17012

AN:

1448402

Hom.:

119

Cov.:

AF XY:

0.0116

AC XY:

8344

AN XY:

721110

show subpopulations

Gnomad4 AFR exome

AF:

0.00175

Gnomad4 AMR exome

AF:

0.00369

Gnomad4 ASJ exome

AF:

0.00227

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00353

Gnomad4 FIN exome

AF:

0.00850

Gnomad4 NFE exome

AF:

0.0140

Gnomad4 OTH exome

AF:

0.00891

GnomAD4 genome

AF:

0.00840

AC:

1280

AN:

152348

Hom.:

Cov.:

AF XY:

0.00809

AC XY:

603

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00219

Gnomad4 AMR

AF:

0.00680

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00856

Gnomad4 NFE

AF:

0.0132

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.0111

Hom.:

Bravo

AF:

0.00838

TwinsUK

AF:

0.0165

AC:

ALSPAC

AF:

0.0171

AC:

ESP6500AA

AF:

0.00187

AC:

ESP6500EA

AF:

0.0130

AC:

107

ExAC

AF:

0.00877

AC:

1059

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 12, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.53

D;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.77

LIST_S2

Pathogenic

0.98

D;T

MetaRNN

Benign

0.010

T;T

MetaSVM

Uncertain

-0.20

MutationAssessor

Benign

1.2

L;L

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-6.0

D;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.0070

D;T

Sift4G

Uncertain

0.010

D;D

Polyphen

0.064

B;P

Vest4

0.34

MVP

0.66

MPC

0.39

ClinPred

0.054

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.51

gMVP

0.62

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over