chr22-20316204-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_033257.4(DGCR6L):c.287T>C(p.Leu96Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
DGCR6L
NM_033257.4 missense
NM_033257.4 missense
Scores
2
9
7
Clinical Significance
Conservation
PhyloP100: 2.39
Genes affected
DGCR6L (HGNC:18551): (DiGeorge syndrome critical region gene 6 like) This gene, the result of a duplication at this locus, is one of two functional genes encoding nearly identical proteins that have similar expression patterns. The product of this gene is a protein that shares homology with the Drosophila gonadal protein, expressed in gonadal tissues and germ cells, and with the human laminin gamma-1 chain that functions in cell attachment and migration. This gene is located in a region of chromosome 22 implicated in the DiGeorge syndrome, one facet of a broader collection of anomalies referred to as the CATCH 22 syndrome. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.855
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DGCR6L | NM_033257.4 | c.287T>C | p.Leu96Pro | missense_variant | 3/5 | ENST00000248879.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DGCR6L | ENST00000248879.8 | c.287T>C | p.Leu96Pro | missense_variant | 3/5 | 1 | NM_033257.4 | P1 | |
DGCR6L | ENST00000443409.1 | c.272-728T>C | intron_variant, NMD_transcript_variant | 1 | |||||
DGCR6L | ENST00000405465.3 | c.259-728T>C | intron_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000864 AC: 2AN: 231564Hom.: 0 AF XY: 0.0000158 AC XY: 2AN XY: 126286
GnomAD3 exomes
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2
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231564
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000206 AC: 3AN: 1453726Hom.: 0 Cov.: 32 AF XY: 0.00000277 AC XY: 2AN XY: 722668
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
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3
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1453726
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32
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
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ExAC
?
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1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 25, 2023 | The c.287T>C (p.L96P) alteration is located in exon 3 (coding exon 3) of the DGCR6L gene. This alteration results from a T to C substitution at nucleotide position 287, causing the leucine (L) at amino acid position 96 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of glycosylation at L96 (P = 0.0075);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at