chr5-126486893-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_023927.4(GRAMD2B):c.1079C>T(p.Ser360Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000031 in 1,610,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
GRAMD2B
NM_023927.4 missense
NM_023927.4 missense
Scores
9
4
4
Clinical Significance
Conservation
PhyloP100: 5.77
Genes affected
GRAMD2B (HGNC:24911): (GRAM domain containing 2B) Enables identical protein binding activity. Located in cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.796
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRAMD2B | NM_023927.4 | c.1079C>T | p.Ser360Leu | missense_variant | 12/14 | ENST00000285689.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRAMD2B | ENST00000285689.8 | c.1079C>T | p.Ser360Leu | missense_variant | 12/14 | 1 | NM_023927.4 | P1 | |
ENST00000648070.1 | n.705-19262G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152010Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000518 AC: 13AN: 251102Hom.: 0 AF XY: 0.0000737 AC XY: 10AN XY: 135678
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GnomAD4 exome AF: 0.0000288 AC: 42AN: 1458944Hom.: 0 Cov.: 28 AF XY: 0.0000372 AC XY: 27AN XY: 726054
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152010Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74224
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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 | Jul 06, 2021 | The c.1124C>T (p.S375L) alteration is located in exon 12 (coding exon 12) of the GRAMD3 gene. This alteration results from a C to T substitution at nucleotide position 1124, causing the serine (S) at amino acid position 375 to be replaced by a leucine (L). 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
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D
Polyphen
1.0
.;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