rs187153114
Variant summary
Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_012330.4(KAT6B):c.1798C>T(p.His600Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,614,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. H600H) has been classified as Likely benign.
Frequency
Consequence
NM_012330.4 missense
Scores
Clinical Significance
Conservation
Publications
- blepharophimosis - intellectual disability syndrome, SBBYS typeInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
- genitopatellar syndromeInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
- KAT6B-related multiple congenital anomalies syndromeInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- RASopathyInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Our verdict: Benign. The variant received -7 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152230Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000239 AC: 6AN: 251292 AF XY: 0.0000221 show subpopulations
GnomAD4 exome AF: 0.0000356 AC: 52AN: 1461872Hom.: 0 Cov.: 32 AF XY: 0.0000344 AC XY: 25AN XY: 727234 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152348Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74498 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Variant summary: KAT6B c.1798C>T (p.His600Tyr) results in a conservative amino acid change in the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change. The variant allele was found at a frequency of 2.4e-05 in 251292 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1798C>T in individuals affected with KAT6B-Related Spectrum Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 260233). Based on the evidence outlined above, the variant was classified as uncertain significance. -
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Genitopatellar syndrome Uncertain:1
This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 600 of the KAT6B protein (p.His600Tyr). This variant is present in population databases (rs187153114, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with KAT6B-related conditions. ClinVar contains an entry for this variant (Variation ID: 260233). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at