chr19-48446764-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_031485.4(GRWD1):c.389A>T(p.Asp130Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,614,048 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: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
GRWD1
NM_031485.4 missense
NM_031485.4 missense
Scores
9
10
Clinical Significance
Conservation
PhyloP100: 7.29
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=0.3768029).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRWD1 | NM_031485.4 | c.389A>T | p.Asp130Val | missense_variant | 3/7 | ENST00000253237.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRWD1 | ENST00000253237.10 | c.389A>T | p.Asp130Val | missense_variant | 3/7 | 1 | NM_031485.4 | P1 | |
GRWD1 | ENST00000598711.1 | c.80A>T | p.Asp27Val | missense_variant | 3/6 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152206Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248882Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134768
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461842Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727220
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74360
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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 | Nov 14, 2023 | The c.389A>T (p.D130V) alteration is located in exon 3 (coding exon 3) of the GRWD1 gene. This alteration results from a A to T substitution at nucleotide position 389, causing the aspartic acid (D) at amino acid position 130 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.
REVEL
Uncertain
Sift
Uncertain
D;.
Sift4G
Uncertain
D;D
Polyphen
B;.
Vest4
MutPred
Gain of sheet (P = 0.0827);.;
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