17-41725047-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_177977.3(HAP1):c.1514C>T(p.Ala505Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,612,234 control chromosomes in the GnomAD database, including 451 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 (no stars).

Frequency

Genomes: 𝑓 0.033 ( 183 hom., cov: 31)

Exomes 𝑓: 0.012 ( 268 hom. )

Consequence

HAP1
NM_177977.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.475

Publications

9 publications found

Variant links:

Genes affected

HAP1 (HGNC:4812): (huntingtin associated protein 1) Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. This gene encodes a protein that interacts with huntingtin, with two cytoskeletal proteins (dynactin and pericentriolar autoantigen protein 1), and with a hepatocyte growth factor-regulated tyrosine kinase substrate. The interactions with cytoskeletal proteins and a kinase substrate suggest a role for this protein in vesicular trafficking or organelle transport. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

HAP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002151817).

BP6

Variant 17-41725047-G-A is Benign according to our data. Variant chr17-41725047-G-A is described in ClinVar as [Benign]. Clinvar id is 3037352.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAP1	NM_177977.3 link	c.1514C>T	p.Ala505Val	missense_variant	Exon 11 of 11	ENST00000347901.9	NP_817084.2	P54257-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAP1	ENST00000347901.9 link	c.1514C>T	p.Ala505Val	missense_variant	Exon 11 of 11	1	NM_177977.3	ENSP00000334002.4		P54257-2

Frequencies

GnomAD3 genomes

AF:

0.0324

AC:

4922

AN:

151956

Hom.:

180

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0895

Gnomad AMI

AF:

0.00989

Gnomad AMR

AF:

0.0195

Gnomad ASJ

AF:

0.0461

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00434

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00937

Gnomad OTH

AF:

0.0287

GnomAD2 exomes

AF:

0.0150

AC:

3768

AN:

251046

AF XY:

0.0134

show subpopulations

Gnomad AFR exome

AF:

0.0943

Gnomad AMR exome

AF:

0.0102

Gnomad ASJ exome

AF:

0.0438

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00281

Gnomad NFE exome

AF:

0.0110

Gnomad OTH exome

AF:

0.0121

GnomAD4 exome

AF:

0.0116

AC:

16952

AN:

1460160

Hom.:

268

Cov.:

AF XY:

0.0112

AC XY:

8130

AN XY:

726474

show subpopulations

African (AFR)

AF:

0.0916

AC:

3063

AN:

33450

American (AMR)

AF:

0.0117

AC:

522

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.0458

AC:

1195

AN:

26110

East Asian (EAS)

AF:

0.000101

AC:

AN:

39664

South Asian (SAS)

AF:

0.00211

AC:

182

AN:

86164

European-Finnish (FIN)

AF:

0.00385

AC:

204

AN:

52928

Middle Eastern (MID)

AF:

0.0182

AC:

105

AN:

5764

European-Non Finnish (NFE)

AF:

0.00966

AC:

10738

AN:

1111076

Other (OTH)

AF:

0.0156

AC:

939

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

943

1885

2828

3770

4713

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0325

AC:

4946

AN:

152074

Hom.:

183

Cov.:

AF XY:

0.0308

AC XY:

2290

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.0898

AC:

3723

AN:

41452

American (AMR)

AF:

0.0195

AC:

298

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0461

AC:

160

AN:

3470

East Asian (EAS)

AF:

0.000194

AC:

AN:

5166

South Asian (SAS)

AF:

0.00145

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00434

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00938

AC:

638

AN:

67990

Other (OTH)

AF:

0.0284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

226

452

678

904

1130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0168

Hom.:

190

Bravo

AF:

0.0369

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.00882

AC:

ESP6500AA

AF:

0.0906

AC:

399

ESP6500EA

AF:

0.0107

AC:

ExAC

AF:

0.0162

AC:

1963

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0109

EpiControl

AF:

0.0129

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HAP1-related disorder

Benign:1

Feb 28, 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

0.11

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.66

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.081

.;.;.;.;.;T

Eigen

Benign

-0.89

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0071

LIST_S2

Benign

0.63

T;T;T;T;T;T

MetaRNN

Benign

0.0022

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

.;.;.;.;.;L

PhyloP100

-0.47

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-2.9

D;D;N;N;N;N

REVEL

Benign

0.045

Sift

Benign

0.13

T;D;T;T;T;T

Sift4G

Benign

0.22

T;D;T;T;T;T

Polyphen

0.017, 0.98, 0.96

.;.;B;D;D;D

Vest4

0.029, 0.069, 0.037, 0.013

MPC

0.36

ClinPred

0.012

GERP RS

-2.2

PromoterAI

-0.011

Neutral

(source)

Varity_R

0.026

gMVP

0.031

Mutation Taster

=100/0

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.

17-41725047-G-A

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