17-41725052-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_177977.3(HAP1):​c.1509G>A​(p.Thr503Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,612,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

HAP1
NM_177977.3 synonymous

Scores

2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0250

Publications

1 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 17-41725052-C-T is Benign according to our data. Variant chr17-41725052-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3038125.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HAP1NM_177977.3 linkc.1509G>A p.Thr503Thr synonymous_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
HAP1ENST00000347901.9 linkc.1509G>A p.Thr503Thr synonymous_variant Exon 11 of 11 1 NM_177977.3 ENSP00000334002.4 P54257-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152150
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000199
AC:
5
AN:
251128
AF XY:
0.0000147
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000959
AC:
14
AN:
1460198
Hom.:
0
Cov.:
35
AF XY:
0.00000826
AC XY:
6
AN XY:
726490
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33450
American (AMR)
AF:
0.00
AC:
0
AN:
44644
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26112
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39662
South Asian (SAS)
AF:
0.0000812
AC:
7
AN:
86162
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53032
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
0.00000540
AC:
6
AN:
1111026
Other (OTH)
AF:
0.00
AC:
0
AN:
60346
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.468
Heterozygous variant carriers
0
2
4
5
7
9
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00000657
AC:
1
AN:
152150
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74310
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41442
American (AMR)
AF:
0.00
AC:
0
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.000193
AC:
1
AN:
5182
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68010
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

HAP1-related disorder Benign:1
May 08, 2019
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

This variant is classified as likely 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
BayesDel_noAF
Benign
-0.68
CADD
Benign
5.0
DANN
Benign
0.58
PhyloP100
0.025
PromoterAI
-0.055
Neutral
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs782272213; hg19: chr17-39881304; COSMIC: COSV57881239; API