chr11-117428356-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_020693.4(DSCAML1):c.6134C>T(p.Ala2045Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000367 in 1,579,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. A2045S) has been classified as Uncertain significance.
Frequency
Consequence
NM_020693.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSCAML1 | NM_020693.4 | c.6134C>T | p.Ala2045Val | missense_variant | 33/33 | ENST00000651296.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSCAML1 | ENST00000651296.2 | c.6134C>T | p.Ala2045Val | missense_variant | 33/33 | NM_020693.4 | |||
DSCAML1 | ENST00000321322.6 | c.6314C>T | p.Ala2105Val | missense_variant | 33/33 | 1 | P1 | ||
DSCAML1 | ENST00000651172.1 | c.6314C>T | p.Ala2105Val | missense_variant | 33/33 | P1 | |||
DSCAML1 | ENST00000527706.5 | c.5504C>T | p.Ala1835Val | missense_variant | 31/31 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000214 AC: 5AN: 233426Hom.: 0 AF XY: 0.0000234 AC XY: 3AN XY: 128260
GnomAD4 exome AF: 0.0000294 AC: 42AN: 1427184Hom.: 0 Cov.: 32 AF XY: 0.0000281 AC XY: 20AN XY: 711196
GnomAD4 genome AF: 0.000105 AC: 16AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74460
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 29, 2024 | The c.6314C>T (p.A2105V) alteration is located in exon 33 (coding exon 33) of the DSCAML1 gene. This alteration results from a C to T substitution at nucleotide position 6314, causing the alanine (A) at amino acid position 2105 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 07, 2023 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 2050912). This variant has not been reported in the literature in individuals affected with DSCAML1-related conditions. This variant is present in population databases (rs146675916, gnomAD 0.007%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2105 of the DSCAML1 protein (p.Ala2105Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at