22-26483980-GGAGGCGGCGCCCCGGGGGAGAGAGGCGGCGCCCCGGGGGAGA-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM4BS2

The NM_001013694.3(SRRD):​c.108_149delGAGAGAGGCGGCGCCCCGGGGGAGAGAGGCGGCGCCCCGGGG​(p.Arg37_Gly50del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000697 in 1,333,678 control chromosomes in the GnomAD database, including 4 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 0)
Exomes 𝑓: 0.00073 ( 4 hom. )

Consequence

SRRD
NM_001013694.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.735

Publications

4 publications found
Variant links:
Genes affected
SRRD (HGNC:33910): (SRR1 domain containing) Predicted to be involved in microtubule-based process; regulation of circadian rhythm; and regulation of heme biosynthetic process. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
HPS4 (HGNC:15844): (HPS4 biogenesis of lysosomal organelles complex 3 subunit 2) This gene encodes a protein component of biogenesis of lysosome-related organelles complexes (BLOC). BLOC complexes are important for the formation of endosomal-lysosomal organelles such as melanosomes and platelet dense granules. Mutations in this gene result in subtype 4 of Hermansky-Pudlak syndrome, a form of albinism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]
HPS4 Gene-Disease associations (from GenCC):
  • Hermansky-Pudlak syndrome 4
    Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • Hermansky-Pudlak syndrome with pulmonary fibrosis
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM4
Nonframeshift variant in NON repetitive region in NM_001013694.3.
BS2
High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SRRDNM_001013694.3 linkc.108_149delGAGAGAGGCGGCGCCCCGGGGGAGAGAGGCGGCGCCCCGGGG p.Arg37_Gly50del disruptive_inframe_deletion Exon 1 of 7 ENST00000215917.11 NP_001013716.2 Q9UH36
HPS4NM_022081.6 linkc.-827_-786delTCTCCCCCGGGGCGCCGCCTCTCTCCCCCGGGGCGCCGCCTC upstream_gene_variant ENST00000398145.7 NP_071364.4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SRRDENST00000215917.11 linkc.108_149delGAGAGAGGCGGCGCCCCGGGGGAGAGAGGCGGCGCCCCGGGG p.Arg37_Gly50del disruptive_inframe_deletion Exon 1 of 7 1 NM_001013694.3 ENSP00000215917.6 Q9UH36
HPS4ENST00000398145.7 linkc.-827_-786delTCTCCCCCGGGGCGCCGCCTCTCTCCCCCGGGGCGCCGCCTC upstream_gene_variant 1 NM_022081.6 ENSP00000381213.2 Q9NQG7-1

Frequencies

GnomAD3 genomes
AF:
0.000447
AC:
65
AN:
145270
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.000278
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000471
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000717
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00228
AC:
22
AN:
9648
AF XY:
0.00204
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000727
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00306
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000728
AC:
865
AN:
1188302
Hom.:
4
AF XY:
0.000726
AC XY:
419
AN XY:
577024
show subpopulations
African (AFR)
AF:
0.000302
AC:
7
AN:
23212
American (AMR)
AF:
0.000682
AC:
7
AN:
10260
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
16558
East Asian (EAS)
AF:
0.000187
AC:
5
AN:
26796
South Asian (SAS)
AF:
0.00117
AC:
61
AN:
51920
European-Finnish (FIN)
AF:
0.000106
AC:
3
AN:
28244
Middle Eastern (MID)
AF:
0.00150
AC:
5
AN:
3344
European-Non Finnish (NFE)
AF:
0.000766
AC:
750
AN:
979508
Other (OTH)
AF:
0.000557
AC:
27
AN:
48460
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.615
Heterozygous variant carriers
0
37
74
111
148
185
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
28
56
84
112
140
<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:
0.000447
AC:
65
AN:
145376
Hom.:
0
Cov.:
0
AF XY:
0.000297
AC XY:
21
AN XY:
70610
show subpopulations
African (AFR)
AF:
0.000277
AC:
11
AN:
39740
American (AMR)
AF:
0.000470
AC:
7
AN:
14898
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3388
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4644
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4486
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
9524
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
286
European-Non Finnish (NFE)
AF:
0.000717
AC:
47
AN:
65542
Other (OTH)
AF:
0.00
AC:
0
AN:
2010
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.520
Heterozygous variant carriers
0
2
4
7
9
11
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome 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
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.73
Mutation Taster
=183/17
polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs66831137; hg19: chr22-26879946; API