rs767235227
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PP2PP3_ModerateBP6
The NM_002473.6(MYH9):c.3903G>C(p.Lys1301Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,613,880 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_002473.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH9 | NM_002473.6 | c.3903G>C | p.Lys1301Asn | missense_variant | 29/41 | ENST00000216181.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH9 | ENST00000216181.11 | c.3903G>C | p.Lys1301Asn | missense_variant | 29/41 | 1 | NM_002473.6 | P1 | |
MYH9 | ENST00000685801.1 | c.3966G>C | p.Lys1322Asn | missense_variant | 30/42 | ||||
MYH9 | ENST00000691109.1 | n.4198G>C | non_coding_transcript_exon_variant | 23/35 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251068Hom.: 1 AF XY: 0.0000221 AC XY: 3AN XY: 135786
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461706Hom.: 1 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727158
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74330
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 21, 2016 | The p.Lys1301Asn variant in MYH9 has not been previously reported in individuals with hearing loss or MYH9-related disorder. This variant has been identified in 1/65600 European chromosomes by the Exome Aggregation Consortium (ExAC, http:// exac.broadinstitute.org; dbSNP rs767235227); however this frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conserv ation analyses do not provide strong support for or against an impact to the pro tein. In summary, the clinical significance of the p.Lys1301Asn variant is uncer tain. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 05, 2022 | The c.3903G>C (p.K1301N) alteration is located in exon 29 (coding exon 28) of the MYH9 gene. This alteration results from a G to C substitution at nucleotide position 3903, causing the lysine (K) at amino acid position 1301 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at