ENST00000396253.7:c.-436C>A

Variant names:

Variant summary

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

The ENST00000396253.7(HPS5):c.-436C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,328 control chromosomes in the GnomAD database, including 1,555 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1554 hom., cov: 32)

Exomes 𝑓: 0.067 ( 1 hom. )

Consequence

HPS5
ENST00000396253.7 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.29

Publications

16 publications found

Variant links:

Genes affected

HPS5 (HGNC:17022): (HPS5 biogenesis of lysosomal organelles complex 2 subunit 2) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. This protein interacts with Hermansky-Pudlak syndrome 6 protein and may interact with the cytoplasmic domain of integrin, alpha-3. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 5. Multiple transcript variants encoding two distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

HPS5 links:

GTF2H1 (HGNC:4655): (general transcription factor IIH subunit 1) Enables thyroid hormone receptor binding activity. Involved in positive regulation of transcription, DNA-templated and transcription by RNA polymerase II. Located in nucleoplasm. Part of transcription factor TFIIH core complex and transcription factor TFIIH holo complex. [provided by Alliance of Genome Resources, Apr 2022]

GTF2H1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000396253.7, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 11-18322147-G-T is Benign according to our data. Variant chr11-18322147-G-T is described in ClinVar as Benign. ClinVar VariationId is 303906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000396253.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HPS5	NM_181507.2	MANE Select	c.-251C>A	upstream_gene	N/A	NP_852608.1	Q9UPZ3-1
HPS5	NM_001440902.1		c.-251C>A	upstream_gene	N/A	NP_001427831.1
HPS5	NM_001440903.1		c.-120C>A	upstream_gene	N/A	NP_001427832.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HPS5	ENST00000396253.7	TSL:1	c.-436C>A	5_prime_UTR	Exon 1 of 22	ENSP00000379552.3	Q9UPZ3-2
HPS5	ENST00000438420.6	TSL:1	c.-249C>A	5_prime_UTR	Exon 1 of 22	ENSP00000399590.2	Q9UPZ3-2
HPS5	ENST00000399287.7	TSL:1	n.32C>A	non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20937

AN:

152030

Hom.:

1551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.0560

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.149

GnomAD4 exome

AF:

0.0667

AC:

AN:

180

Hom.:

Cov.:

AF XY:

0.0870

AC XY:

AN XY:

138

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.125

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0455

AC:

AN:

132

Other (OTH)

AF:

0.0714

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.138

AC:

20949

AN:

152148

Hom.:

1554

Cov.:

AF XY:

0.140

AC XY:

10440

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.187

AC:

7769

AN:

41504

American (AMR)

AF:

0.154

AC:

2359

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.123

AC:

428

AN:

3472

East Asian (EAS)

AF:

0.118

AC:

607

AN:

5156

South Asian (SAS)

AF:

0.116

AC:

559

AN:

4826

European-Finnish (FIN)

AF:

0.176

AC:

1858

AN:

10580

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.102

AC:

6966

AN:

68002

Other (OTH)

AF:

0.147

AC:

312

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

929

1858

2787

3716

4645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

222

444

666

888

1110

<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:

0.114

Hom.:

1232

Bravo

AF:

0.139

Asia WGS

AF:

0.137

AC:

478

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hermansky-Pudlak syndrome 5 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.1

(source)

DANN

Benign

0.68

PhyloP100

-1.3

PromoterAI

-0.091

Neutral

(source)

Mutation Taster

=300/0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over