chr22-18910993-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_005675.6(DGCR6):c.478G>A(p.Gly160Arg) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 0)
Consequence
DGCR6
NM_005675.6 missense
NM_005675.6 missense
Scores
12
3
2
Clinical Significance
Conservation
PhyloP100: 7.88
Genes affected
DGCR6 (HGNC:2846): (DiGeorge syndrome critical region gene 6) DiGeorge syndrome, and more widely, the CATCH 22 syndrome, are associated with microdeletions in chromosomal region 22q11.2. The product of this gene shares homology with the Drosophila melanogaster gonadal protein, which participates in gonadal and germ cell development, and with the gamma-1 subunit of human laminin. This gene is a candidate for involvement in DiGeorge syndrome pathology and in schizophrenia. [provided by RefSeq, Nov 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.896
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DGCR6 | NM_005675.6 | c.478G>A | p.Gly160Arg | missense_variant | 4/5 | ENST00000331444.12 | |
DGCR6 | XM_047441510.1 | c.271G>A | p.Gly91Arg | missense_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DGCR6 | ENST00000331444.12 | c.478G>A | p.Gly160Arg | missense_variant | 4/5 | 1 | NM_005675.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 0
GnomAD3 genomes
?
Cov.:
0
GnomAD3 exomes AF: 0.0000404 AC: 10AN: 247434Hom.: 0 AF XY: 0.0000447 AC XY: 6AN XY: 134198
GnomAD3 exomes
AF:
AC:
10
AN:
247434
Hom.:
AF XY:
AC XY:
6
AN XY:
134198
Gnomad AFR exome
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GnomAD4 exome Cov.: 0
GnomAD4 exome
Cov.:
0
GnomAD4 genome ? Cov.: 0
GnomAD4 genome
?
Cov.:
0
Alfa
AF:
Hom.:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
1
ExAC
?
AF:
AC:
5
EpiCase
AF:
EpiControl
AF:
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 | Aug 17, 2021 | The c.478G>A (p.G160R) alteration is located in exon 4 (coding exon 4) of the DGCR6 gene. This alteration results from a G to A substitution at nucleotide position 478, causing the glycine (G) at amino acid position 160 to be replaced by an arginine (R). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;.;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;.
Sift
Pathogenic
D;D;.
Sift4G
Pathogenic
D;D;.
Polyphen
1.0
.;D;.
Vest4
MutPred
0.78
.;Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);
MVP
MPC
0.56
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