chr19-48450680-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_031485.4(GRWD1):c.697G>A(p.Gly233Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000316 in 1,613,804 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000032 ( 0 hom. )
Consequence
GRWD1
NM_031485.4 missense
NM_031485.4 missense
Scores
9
6
4
Clinical Significance
Conservation
PhyloP100: 6.60
Genes affected
GRWD1 (HGNC:21270): (glutamate rich WD repeat containing 1) This gene encodes a glutamate-rich protein that contains five WD-repeat motifs. The encoded protein may play a critical role in ribosome biogenesis and may also play a role in histone methylation through interactions with CUL4-DDB1 ubiquitin E3 ligase. [provided by RefSeq, Feb 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRWD1 | NM_031485.4 | c.697G>A | p.Gly233Ser | missense_variant | 5/7 | ENST00000253237.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRWD1 | ENST00000253237.10 | c.697G>A | p.Gly233Ser | missense_variant | 5/7 | 1 | NM_031485.4 | P1 | |
GRWD1 | ENST00000598711.1 | c.388G>A | p.Gly130Ser | missense_variant | 5/6 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152150Hom.: 0 Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000360 AC: 9AN: 250290Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135438
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GnomAD4 exome AF: 0.0000322 AC: 47AN: 1461536Hom.: 0 Cov.: 33 AF XY: 0.0000330 AC XY: 24AN XY: 727070
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152268Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3AN XY: 74432
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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 | Oct 10, 2023 | The c.697G>A (p.G233S) alteration is located in exon 5 (coding exon 5) of the GRWD1 gene. This alteration results from a G to A substitution at nucleotide position 697, causing the glycine (G) at amino acid position 233 to be replaced by a serine (S). 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
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
H;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.
REVEL
Uncertain
Sift
Pathogenic
D;.
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at