11-123577563-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001387025.1(GRAMD1B):c.649G>A(p.Gly217Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000252 in 1,586,236 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 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
GRAMD1B
NM_001387025.1 missense
NM_001387025.1 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: 4.37
Genes affected
GRAMD1B (HGNC:29214): (GRAM domain containing 1B) Predicted to enable cholesterol binding activity; cholesterol transfer activity; and phospholipid binding activity. Predicted to be involved in cellular response to cholesterol and cholesterol homeostasis. Located in endoplasmic reticulum membrane; endoplasmic reticulum-plasma membrane contact site; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08890298).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GRAMD1B | NM_001387025.1 | c.649G>A | p.Gly217Ser | missense_variant | 3/20 | ENST00000635736.2 | NP_001373954.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GRAMD1B | ENST00000635736.2 | c.649G>A | p.Gly217Ser | missense_variant | 3/20 | 5 | NM_001387025.1 | ENSP00000490062 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152246Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000511 AC: 1AN: 195654Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 106232
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GnomAD4 exome AF: 0.00000209 AC: 3AN: 1433990Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 710986
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152246Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74378
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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 | Jan 09, 2024 | The c.220G>A (p.G74S) alteration is located in exon 2 (coding exon 2) of the GRAMD1B gene. This alteration results from a G to A substitution at nucleotide position 220, causing the glycine (G) at amino acid position 74 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
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.;T;.;.;T;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;T;T;D;T;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
.;.;.;.;.;.;N;N;N;N;N
REVEL
Benign
Sift
Benign
.;.;.;.;.;.;T;T;T;T;T
Sift4G
Benign
.;.;T;T;.;T;T;T;T;T;T
Polyphen
0.019
.;.;.;.;.;.;.;.;B;.;.
Vest4
0.14, 0.16, 0.14, 0.16
MutPred
0.26
.;.;.;.;.;.;Gain of phosphorylation at G74 (P = 0.0019);Gain of phosphorylation at G74 (P = 0.0019);Gain of phosphorylation at G74 (P = 0.0019);.;.;
MVP
0.043
MPC
1.6
ClinPred
T
GERP RS
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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