chr17-4539966-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_014520.4(MYBBP1A):c.3436C>T(p.Arg1146Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000168 in 1,597,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1146H) has been classified as Uncertain significance.
Frequency
Consequence
NM_014520.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYBBP1A | NM_014520.4 | c.3436C>T | p.Arg1146Cys | missense_variant, splice_region_variant | 26/26 | ENST00000254718.9 | |
MYBBP1A | NM_001105538.2 | c.3436C>T | p.Arg1146Cys | missense_variant, splice_region_variant | 26/27 | ||
MYBBP1A | XM_024450536.2 | c.3299C>T | p.Ala1100Val | missense_variant, splice_region_variant | 25/25 | ||
MYBBP1A | XM_011523616.3 | c.2680C>T | p.Arg894Cys | missense_variant, splice_region_variant | 21/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYBBP1A | ENST00000254718.9 | c.3436C>T | p.Arg1146Cys | missense_variant, splice_region_variant | 26/26 | 1 | NM_014520.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000283 AC: 43AN: 152160Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000238 AC: 56AN: 235382Hom.: 0 AF XY: 0.000209 AC XY: 27AN XY: 129144
GnomAD4 exome AF: 0.000156 AC: 226AN: 1445594Hom.: 0 Cov.: 36 AF XY: 0.000168 AC XY: 121AN XY: 719356
GnomAD4 genome ? AF: 0.000282 AC: 43AN: 152278Hom.: 0 Cov.: 31 AF XY: 0.000228 AC XY: 17AN XY: 74446
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 08, 2022 | The c.3436C>T (p.R1146C) alteration is located in exon 26 (coding exon 26) of the MYBBP1A gene. This alteration results from a C to T substitution at nucleotide position 3436, causing the arginine (R) at amino acid position 1146 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at