rs59328451
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_005557.4(KRT16):c.1062A>T(p.Lys354Asn) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000177 in 1,612,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 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_005557.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRT16 | NM_005557.4 | c.1062A>T | p.Lys354Asn | missense_variant, splice_region_variant | 6/8 | ENST00000301653.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRT16 | ENST00000301653.9 | c.1062A>T | p.Lys354Asn | missense_variant, splice_region_variant | 6/8 | 1 | NM_005557.4 | P1 | |
KRT16 | ENST00000593067.1 | c.348A>T | p.Lys116Asn | missense_variant, splice_region_variant | 7/7 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00101 AC: 153AN: 152210Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000249 AC: 62AN: 249348Hom.: 0 AF XY: 0.000192 AC XY: 26AN XY: 135344
GnomAD4 exome AF: 0.0000856 AC: 125AN: 1459714Hom.: 0 Cov.: 35 AF XY: 0.0000716 AC XY: 52AN XY: 726172
GnomAD4 genome ? AF: 0.00105 AC: 160AN: 152328Hom.: 0 Cov.: 32 AF XY: 0.00118 AC XY: 88AN XY: 74490
ClinVar
Submissions by phenotype
not provided Pathogenic:1Benign:1Other:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Oct 06, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 11359398, 30859684, 31589614) - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 13, 2023 | - - |
not provided, no classification provided | literature only | Epithelial Biology; Institute of Medical Biology, Singapore | - | - - |
Pachyonychia congenita 1 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2001 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 29, 2024 | The p.Lys354Asn variant in KRT16 is classified as likely benign because it has been identified in 0.35% (149/41448) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org, v.3.1.2). ACMG/AMP Criteria applied: BS1. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at