rs7122032

Variant names:

• chr11-18306101-T-A
• NM_181507.2:c.824+34A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-18306101-T-A
• chr11-18306101-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181507.2(HPS5):​c.824+34A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000779 in 1,283,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: HPS5 NM_181507.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPS5	NM_181507.2	c.824+34A>T		intron_variant	Intron 7 of 22	ENST00000349215.8	NP_852608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPS5	ENST00000349215.8	c.824+34A>T		intron_variant	Intron 7 of 22	1	NM_181507.2	ENSP00000265967.5
HPS5	ENST00000396253.7	c.482+34A>T		intron_variant	Intron 6 of 21	1		ENSP00000379552.3
HPS5	ENST00000438420.6	c.482+34A>T		intron_variant	Intron 6 of 21	1		ENSP00000399590.2
HPS5	ENST00000531848.1	c.482+34A>T		intron_variant	Intron 6 of 10	5		ENSP00000431758.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.79e-7 AC: 1 AN: 1283042 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 647626

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000105

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.4
DANN	Benign	0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-18327648;