chr19-48450737-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_031485.4(GRWD1):c.754G>A(p.Val252Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,772 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 (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
GRWD1
NM_031485.4 missense
NM_031485.4 missense
Scores
3
7
9
Clinical Significance
Conservation
PhyloP100: 4.60
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 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.31447017).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRWD1 | NM_031485.4 | c.754G>A | p.Val252Met | missense_variant | 5/7 | ENST00000253237.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRWD1 | ENST00000253237.10 | c.754G>A | p.Val252Met | missense_variant | 5/7 | 1 | NM_031485.4 | P1 | |
GRWD1 | ENST00000598711.1 | c.445G>A | p.Val149Met | missense_variant | 5/6 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250724Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135634
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461772Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 727196
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
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 | Mar 16, 2022 | The c.754G>A (p.V252M) 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 754, causing the valine (V) at amino acid position 252 to be replaced by a methionine (M). 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
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.
REVEL
Benign
Sift
Uncertain
D;.
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Loss of catalytic residue at V252 (P = 0.0688);.;
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