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2-233309220-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_000541.5(SAG):c.31G>A(p.Glu11Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 152168 control chromosomes in the gnomAD Genomes database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00041 ( 0 hom. )

Consequence

SAG
NM_000541.5 missense

Scores

16

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:1

Conservation

PhyloP100: -0.376

Links

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
?
Computational evidence support a benign effect (MetaRNN=0.004472792).
BP6
?
Variant 2-233309220-G-A is Benign according to our data. Variant chr2-233309220-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 791237.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SAGNM_000541.5 linkuse as main transcriptc.31G>A p.Glu11Lys missense_variant 2/16 ENST00000409110.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SAGENST00000409110.6 linkuse as main transcriptc.31G>A p.Glu11Lys missense_variant 2/165 NM_000541.5 P1

Frequencies

GnomAD3 genomes
AF:
0.00121
AC:
184
AN:
152168
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00367
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000982
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000406
AC:
101
AN:
249016
Hom.:
0
AF XY:
0.000370
AC XY:
50
AN XY:
135092
show subpopulations
Gnomad AFR exome
AF:
0.00297
Gnomad AMR exome
AF:
0.000609
Gnomad ASJ exome
AF:
0.000597
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000195
Gnomad OTH exome
AF:
0.000993
GnomAD4 exome
AF:
0.000231
AC:
338
AN:
1461490
Hom.:
1
AF XY:
0.000212
AC XY:
154
AN XY:
727026
show subpopulations
Gnomad4 AFR exome
AF:
0.00284
Gnomad4 AMR exome
AF:
0.000649
Gnomad4 ASJ exome
AF:
0.000804
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000113
Gnomad4 OTH exome
AF:
0.000944
Alfa
AF:
0.000338
Hom.:
0
Bravo
AF:
0.00140
ESP6500AA
AF:
0.00183
AC:
7
ESP6500EA
AF:
0.000242
AC:
2
ExAC
AF:
0.000315
AC:
38
EpiCase
AF:
0.000218
EpiControl
AF:
0.000119

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:4Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:2Benign:1
Uncertain significance, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
Uncertain significance, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
Likely benign, criteria provided, single submitterclinical testingInvitaeNov 01, 2022- -
Oguchi disease Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Retinitis pigmentosa Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.61
T
BayesDel_noAF
Benign
-0.65
Cadd
Benign
0.25
Dann
Benign
0.20
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.0091
N
M_CAP
Benign
0.0045
T
MetaRNN
Benign
0.0045
T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
0.010
N;N;N
REVEL
Benign
0.098
Sift
Benign
1.0
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.022
.;B;.
Vest4
0.17
MVP
0.31
MPC
0.14
ClinPred
0.0050
T
GERP RS
-3.2
Varity_R
0.024
gMVP
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200078242; hg19: chr2-234217866; API