10-99880058-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_015221.4(DNMBP):c.4301G>A(p.Cys1434Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,614,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_015221.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNMBP | NM_015221.4 | c.4301G>A | p.Cys1434Tyr | missense_variant | 16/17 | ENST00000324109.9 | NP_056036.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNMBP | ENST00000324109.9 | c.4301G>A | p.Cys1434Tyr | missense_variant | 16/17 | 1 | NM_015221.4 | ENSP00000315659 | P1 | |
DNMBP | ENST00000543621.6 | c.2165G>A | p.Cys722Tyr | missense_variant | 13/14 | 1 | ENSP00000443657 | |||
DNMBP | ENST00000636706.1 | c.3197G>A | p.Cys1066Tyr | missense_variant | 13/14 | 2 | ENSP00000489875 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152148Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251486Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135918
GnomAD4 exome AF: 0.0000499 AC: 73AN: 1461878Hom.: 0 Cov.: 53 AF XY: 0.0000440 AC XY: 32AN XY: 727238
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152148Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74330
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 20, 2022 | The c.4301G>A (p.C1434Y) alteration is located in exon 16 (coding exon 15) of the DNMBP gene. This alteration results from a G to A substitution at nucleotide position 4301, causing the cysteine (C) at amino acid position 1434 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The DNMBP p.Cys1066Tyr variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs371661794) and LOVD 3.0 (variant effect not shared). The variant was identified in control databases in 5 of 282878 chromosomes at a frequency of 0.00001768 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the European (non-Finnish) population in 5 of 129190 chromosomes (freq: 0.000039), but was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other, or South Asian populations. The p.Cys1066 residue is conserved in mammals but not in more distantly related organisms however four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at