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GeneBe

2-233309241-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PM2_Supporting

The NM_000541.5(SAG):c.52A>G(p.Lys18Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD Genomes project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SAG
NM_000541.5 missense

Scores

2
9
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.83

Links

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
?
Very rare variant; Number of alleles below threshold, Median coverage is 32.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SAGNM_000541.5 linkuse as main transcriptc.52A>G p.Lys18Glu missense_variant 2/16 ENST00000409110.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SAGENST00000409110.6 linkuse as main transcriptc.52A>G p.Lys18Glu missense_variant 2/165 NM_000541.5 P1

Frequencies

GnomAD3 genomes
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeMay 10, 2022This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 18 of the SAG protein (p.Lys18Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SAG-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Uncertain
0.084
D
BayesDel_noAF
Benign
-0.12
Cadd
Uncertain
24
Dann
Uncertain
1.0
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Uncertain
0.90
D
M_CAP
Benign
0.020
T
MetaRNN
Uncertain
0.45
T;T;T
MetaSVM
Benign
-0.96
T
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.65
T
PROVEAN
Uncertain
-3.6
D;D;D
REVEL
Benign
0.24
Sift
Pathogenic
0.0
D;D;D
Sift4G
Uncertain
0.0020
D;D;D
Polyphen
0.90
.;P;.
Vest4
0.76
MutPred
0.58
Loss of methylation at K18 (P = 3e-04);Loss of methylation at K18 (P = 3e-04);Loss of methylation at K18 (P = 3e-04);
MVP
0.41
MPC
0.53
ClinPred
0.99
D
GERP RS
3.3
Varity_R
0.90
gMVP
0.78

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-234217887; API