rs3816

Variant names:

• chr10-102067980-T-A
• rs3816
• NM_024747.6:c.*178T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-102067980-T-A
• chr10-102067980-T-C
• chr10-102067980-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024747.6(HPS6):​c.*178T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000036 in 555,286 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: 0.0000036 (0 hom.)
• Consequence: HPS6 NM_024747.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.514
• Publications: 0 publications found

Genes affected

HPS6 (HGNC:18817): (HPS6 biogenesis of lysosomal organelles complex 2 subunit 3) This intronless 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 5 protein. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 6. [provided by RefSeq, Jul 2008]

HPS6 Gene-Disease associations (from GenCC):

• Hermansky-Pudlak syndrome 6

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• Hermansky-Pudlak syndrome without pulmonary fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPS6	NM_024747.6	c.*178T>A		3_prime_UTR_variant	Exon 1 of 1	ENST00000299238.7	NP_079023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPS6	ENST00000299238.7	c.*178T>A		3_prime_UTR_variant	Exon 1 of 1	6	NM_024747.6	ENSP00000299238.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000360 AC: 2 AN: 555286 Hom.: 0 Cov.: 6 AF XY: 0.00000337 AC XY: 1 AN XY: 296656

African (AFR) AF: 0.00 AC: 0 AN: 14906

American (AMR) AF: 0.00 AC: 0 AN: 29874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18092

East Asian (EAS) AF: 0.00 AC: 0 AN: 31786

South Asian (SAS) AF: 0.00 AC: 0 AN: 59166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46852

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3142

European-Non Finnish (NFE) AF: 0.00000622 AC: 2 AN: 321714

Other (OTH) AF: 0.00 AC: 0 AN: 29754

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.51
PhyloP100		0.51

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

Other links and lift over

dbSNP: rs3816; hg19: chr10-103827737;