chr12-100622288-C-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_174942.3(GAS2L3):āc.662C>Gā(p.Ala221Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 1,435,710 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 31)
Exomes š: 0.0000028 ( 0 hom. )
Consequence
GAS2L3
NM_174942.3 missense
NM_174942.3 missense
Scores
2
7
9
Clinical Significance
Conservation
PhyloP100: 2.55
Genes affected
GAS2L3 (HGNC:27475): (growth arrest specific 2 like 3) Enables actin binding activity and microtubule binding activity. Involved in actin cytoskeleton organization and microtubule cytoskeleton organization. Located in actin cytoskeleton and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]
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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 |
---|---|---|---|---|---|---|---|
GAS2L3 | NM_174942.3 | c.662C>G | p.Ala221Gly | missense_variant | 9/10 | ENST00000547754.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAS2L3 | ENST00000547754.6 | c.662C>G | p.Ala221Gly | missense_variant | 9/10 | 1 | NM_174942.3 | P1 | |
GAS2L3 | ENST00000266754.9 | c.662C>G | p.Ala221Gly | missense_variant | 8/9 | 1 | P1 | ||
GAS2L3 | ENST00000539410.2 | c.662C>G | p.Ala221Gly | missense_variant | 7/8 | 2 | P1 | ||
GAS2L3 | ENST00000537247.5 | c.350C>G | p.Ala117Gly | missense_variant | 9/10 | 2 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248592Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134316
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GnomAD4 exome AF: 0.00000279 AC: 4AN: 1435710Hom.: 0 Cov.: 25 AF XY: 0.00000140 AC XY: 1AN XY: 715666
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GnomAD4 genome Cov.: 31
GnomAD4 genome
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31
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 | Dec 16, 2021 | The c.662C>G (p.A221G) alteration is located in exon 9 (coding exon 7) of the GAS2L3 gene. This alteration results from a C to G substitution at nucleotide position 662, causing the alanine (A) at amino acid position 221 to be replaced by a glycine (G). 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
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;L
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Benign
T;T;D;T
Polyphen
D;D;.;D
Vest4
MutPred
Gain of catalytic residue at P225 (P = 2e-04);Gain of catalytic residue at P225 (P = 2e-04);.;Gain of catalytic residue at P225 (P = 2e-04);
MVP
MPC
0.42
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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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