rs191171943
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_016239.4(MYO15A):c.7655-7C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000357 in 1,614,204 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_016239.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.7655-7C>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000647165.2 | |||
LOC124903944 | XR_007065652.1 | n.377+215G>C | intron_variant, non_coding_transcript_variant | ||||
MYO15A | XM_017024714.3 | c.7595-7C>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
MYO15A | XM_017024715.3 | c.7658-7C>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO15A | ENST00000647165.2 | c.7655-7C>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NM_016239.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00192 AC: 293AN: 152216Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000501 AC: 125AN: 249496Hom.: 0 AF XY: 0.000428 AC XY: 58AN XY: 135384
GnomAD4 exome AF: 0.000194 AC: 283AN: 1461870Hom.: 1 Cov.: 37 AF XY: 0.000172 AC XY: 125AN XY: 727236
GnomAD4 genome ? AF: 0.00193 AC: 294AN: 152334Hom.: 0 Cov.: 33 AF XY: 0.00196 AC XY: 146AN XY: 74494
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 25, 2017 | c.7655-7C>G in intron 39 of MYO15A: This variant is not expected to have clinica l significance because it has been identified in 0.6% (59/9796) of African chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNP rs191171943). - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 19, 2018 | The c.7655-7 C>G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant is observed in 162/24020 (0.674%) alleles from individuals of African background in large population cohorts (Lek et al., 2016). Several in silico splice prediction models predict that c.7655-7 C>G damages the natural splice acceptor site and leads to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. - |
Autosomal recessive nonsyndromic hearing loss 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jul 15, 2022 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at