rs17740607

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.92C>T(p.Thr31Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0941 in 1,613,916 control chromosomes in the GnomAD database, including 7,909 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 652 hom., cov: 32)

Exomes 𝑓: 0.096 ( 7257 hom. )

Consequence

HDC
NM_002112.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.28

Publications

32 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=0.0017606616).

BP6

Variant 15-50263347-G-A is Benign according to our data. Variant chr15-50263347-G-A is described in ClinVar as Benign. ClinVar VariationId is 1227379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDC	NM_002112.4 link	c.92C>T	p.Thr31Met	missense_variant	Exon 2 of 12	ENST00000267845.8	NP_002103.2	P19113-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDC	ENST00000267845.8 link	c.92C>T	p.Thr31Met	missense_variant	Exon 2 of 12	1	NM_002112.4	ENSP00000267845.3		P19113-1

Frequencies

GnomAD3 genomes

AF:

0.0785

AC:

11950

AN:

152144

Hom.:

654

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0193

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.0878

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.0477

Gnomad SAS

AF:

0.0366

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0845

GnomAD2 exomes

AF:

0.0852

AC:

21397

AN:

251182

AF XY:

0.0858

show subpopulations

Gnomad AFR exome

AF:

0.0175

Gnomad AMR exome

AF:

0.0659

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.0571

Gnomad FIN exome

AF:

0.121

Gnomad NFE exome

AF:

0.108

Gnomad OTH exome

AF:

0.0916

GnomAD4 exome

AF:

0.0958

AC:

139958

AN:

1461654

Hom.:

7257

Cov.:

AF XY:

0.0949

AC XY:

69034

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.0167

AC:

560

AN:

33476

American (AMR)

AF:

0.0684

AC:

3058

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.113

AC:

2963

AN:

26136

East Asian (EAS)

AF:

0.0344

AC:

1365

AN:

39700

South Asian (SAS)

AF:

0.0400

AC:

3448

AN:

86256

European-Finnish (FIN)

AF:

0.116

AC:

6208

AN:

53360

Middle Eastern (MID)

AF:

0.115

AC:

666

AN:

5768

European-Non Finnish (NFE)

AF:

0.105

AC:

116234

AN:

1111844

Other (OTH)

AF:

0.0903

AC:

5456

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

6890

13781

20671

27562

34452

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4078

8156

12234

16312

20390

<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:

0.0785

AC:

11946

AN:

152262

Hom.:

652

Cov.:

AF XY:

0.0791

AC XY:

5887

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0193

AC:

801

AN:

41566

American (AMR)

AF:

0.0878

AC:

1342

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.118

AC:

409

AN:

3472

East Asian (EAS)

AF:

0.0476

AC:

247

AN:

5186

South Asian (SAS)

AF:

0.0358

AC:

173

AN:

4828

European-Finnish (FIN)

AF:

0.123

AC:

1302

AN:

10588

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7362

AN:

68020

Other (OTH)

AF:

0.0836

AC:

177

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

573

1146

1719

2292

2865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

142

284

426

568

710

<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:

0.0932

Hom.:

2288

Bravo

AF:

0.0724

TwinsUK

AF:

0.104

AC:

386

ALSPAC

AF:

0.102

AC:

392

ESP6500AA

AF:

0.0257

AC:

113

ESP6500EA

AF:

0.113

AC:

972

ExAC

AF:

0.0836

AC:

10146

Asia WGS

AF:

0.0370

AC:

129

AN:

3478

EpiCase

AF:

0.106

EpiControl

AF:

0.109

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 29, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 25846768) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

HDC-related disorder

Benign:1

Oct 22, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;.;.

Eigen

Benign

-0.037

Eigen_PC

Benign

-0.015

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.97

D;D;D

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;L;.

PhyloP100

1.3

PrimateAI

Benign

0.37

PROVEAN

Benign

0.15

N;N;N

REVEL

Benign

0.047

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.12

T;T;.

Polyphen

0.97

D;.;.

Vest4

0.31

MPC

0.43

ClinPred

0.011

GERP RS

3.0

PromoterAI

-0.028

Neutral

(source)

Varity_R

0.053

gMVP

0.75

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