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GeneBe

2-233309256-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PM2_SupportingBP4

The NM_000541.5(SAG):c.67G>C(p.Asp23His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SAG
NM_000541.5 missense

Scores

1
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.10

Links

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance.

PM2
?
Very rare variant; Number of alleles below threshold, Median coverage is 32.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.33165437).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SAGNM_000541.5 linkuse as main transcriptc.67G>C p.Asp23His missense_variant 2/16 ENST00000409110.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SAGENST00000409110.6 linkuse as main transcriptc.67G>C p.Asp23His 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 testingInvitaeAug 23, 2022This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 23 of the SAG protein (p.Asp23His). 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: "Probably 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
0.97
BayesDel_addAF
Benign
-0.021
T
BayesDel_noAF
Benign
-0.27
Cadd
Pathogenic
26
Dann
Uncertain
1.0
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.92
D
M_CAP
Benign
0.0076
T
MetaRNN
Benign
0.33
T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-2.1
N;N;D
REVEL
Benign
0.21
Sift
Uncertain
0.0010
D;D;D
Sift4G
Uncertain
0.022
D;D;D
Polyphen
1.0
.;D;.
Vest4
0.68
MutPred
0.40
Loss of stability (P = 0.0289);Loss of stability (P = 0.0289);Loss of stability (P = 0.0289);
MVP
0.49
MPC
0.62
ClinPred
0.97
D
GERP RS
3.6
Varity_R
0.49
gMVP
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: chr2-234217902; API