3-149141387-A-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_032383.5(HPS3):c.970+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0377 in 1,606,870 control chromosomes in the GnomAD database, including 1,367 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_032383.5 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HPS3 | ENST00000296051.7 | c.970+7A>G | splice_region_variant, intron_variant | Intron 4 of 16 | 1 | NM_032383.5 | ENSP00000296051.2 | |||
HPS3 | ENST00000460120.5 | c.475+7A>G | splice_region_variant, intron_variant | Intron 3 of 15 | 2 | ENSP00000418230.1 | ||||
HPS3 | ENST00000462030.5 | n.1569+7A>G | splice_region_variant, intron_variant | Intron 4 of 6 | 2 | |||||
HPS3 | ENST00000486530.1 | n.1003+7A>G | splice_region_variant, intron_variant | Intron 4 of 6 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0270 AC: 4103AN: 152104Hom.: 75 Cov.: 31
GnomAD3 exomes AF: 0.0346 AC: 8698AN: 251228Hom.: 223 AF XY: 0.0385 AC XY: 5226AN XY: 135790
GnomAD4 exome AF: 0.0388 AC: 56481AN: 1454650Hom.: 1293 Cov.: 31 AF XY: 0.0400 AC XY: 28950AN XY: 724138
GnomAD4 genome AF: 0.0269 AC: 4098AN: 152220Hom.: 74 Cov.: 31 AF XY: 0.0276 AC XY: 2058AN XY: 74448
ClinVar
Submissions by phenotype
not specified Benign:3
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970+7A>G in intron 4 of HPS3: This variant is not expected to have clinical sign ificance because it is not located within the conserved splice consensus sequenc e. It has been identified in 3.6% (309/8600) of European American chromosomes fr om a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washi ngton.edu/EVS; dbSNP rs114029765). -
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Hermansky-Pudlak syndrome 3 Benign:3
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
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not provided Benign:2
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Hermansky-Pudlak syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at