dbSNP rs16963486: HDC:p.Phe553Leu (chr15-50242592-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002112.4(HDC):c.1657T>C(p.Phe553Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00389 in 1,614,148 control chromosomes in the GnomAD database, including 194 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 102 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 92 hom. )

Consequence

HDC
NM_002112.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.74

Publications

8 publications found

Variant links:

Genes affected

HDC (HGNC:4855): (histidine decarboxylase) This gene encodes a member of the group II decarboxylase family and forms a homodimer that converts L-histidine to histamine in a pyridoxal phosphate dependent manner. Histamine regulates several physiologic processes, including neurotransmission, gastric acid secretion,inflamation, and smooth muscle tone.[provided by RefSeq, Aug 2010]

HDC Gene-Disease associations (from GenCC):

Tourette syndrome
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

HDC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043698847).

BP6

Variant 15-50242592-A-G is Benign according to our data. Variant chr15-50242592-A-G is described in ClinVar as Benign. ClinVar VariationId is 776888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDC	NM_002112.4 link	c.1657T>C	p.Phe553Leu	missense_variant	Exon 12 of 12	ENST00000267845.8	NP_002103.2	P19113-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HDC	ENST00000267845.8 link	c.1657T>C	p.Phe553Leu	missense_variant	Exon 12 of 12	1	NM_002112.4	ENSP00000267845.3	P19113-1
HDC	ENST00000543581.5 link	c.1558T>C	p.Phe520Leu	missense_variant	Exon 11 of 11	1		ENSP00000440252.1	P19113-2
HDC	ENST00000559816.1 link	n.1401T>C		non_coding_transcript_exon_variant	Exon 5 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.0206

AC:

3135

AN:

152140

Hom.:

101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0729

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0120

GnomAD2 exomes

AF:

0.00522

AC:

1312

AN:

251482

AF XY:

0.00391

show subpopulations

Gnomad AFR exome

AF:

0.0714

Gnomad AMR exome

AF:

0.00321

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000193

Gnomad OTH exome

AF:

0.00195

GnomAD4 exome

AF:

0.00214

AC:

3131

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

1342

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.0756

AC:

2530

AN:

33480

American (AMR)

AF:

0.00324

AC:

145

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000151

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000998

AC:

111

AN:

1112008

Other (OTH)

AF:

0.00517

AC:

312

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

201

402

602

803

1004

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

252

336

420

<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:

0.0207

AC:

3153

AN:

152258

Hom.:

102

Cov.:

AF XY:

0.0198

AC XY:

1475

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0731

AC:

3035

AN:

41524

American (AMR)

AF:

0.00471

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68028

Other (OTH)

AF:

0.0118

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

147

294

440

587

734

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.00680

Hom.:

110

Bravo

AF:

0.0233

ESP6500AA

AF:

0.0726

AC:

319

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00669

AC:

812

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

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

- -

Dec 31, 2019

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

Uncertain

0.56

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

T;T

MetaRNN

Benign

0.0044

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.1

M;.

PhyloP100

6.7

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.16

Sift

Uncertain

0.0080

D;D

Sift4G

Benign

0.64

T;T

Polyphen

0.98

D;.

Vest4

0.60

MutPred

0.22

Gain of helix (P = 0.0325);.;

MVP

0.42

MPC

0.75

ClinPred

0.022

GERP RS

5.7

Varity_R

0.19

gMVP

0.32

Mutation Taster

=99/1

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over