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GeneBe

2-233309224-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_000541.5(SAG):c.35C>T(p.Pro12Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000342 in 152066 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P12P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00058 ( 1 hom. )

Consequence

SAG
NM_000541.5 missense

Scores

3
13

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0770

Links

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
?
Computational evidence support a benign effect (MetaRNN=0.02061376).
BP6
?
Variant 2-233309224-C-T is Benign according to our data. Variant chr2-233309224-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1088116.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-233309224-C-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SAGNM_000541.5 linkuse as main transcriptc.35C>T p.Pro12Leu missense_variant 2/16 ENST00000409110.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SAGENST00000409110.6 linkuse as main transcriptc.35C>T p.Pro12Leu missense_variant 2/165 NM_000541.5 P1

Frequencies

GnomAD3 genomes
AF:
0.000342
AC:
52
AN:
152066
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000945
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000617
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000582
AC:
145
AN:
249040
Hom.:
1
AF XY:
0.000592
AC XY:
80
AN XY:
135110
show subpopulations
Gnomad AFR exome
AF:
0.000129
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000111
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000371
Gnomad NFE exome
AF:
0.00111
Gnomad OTH exome
AF:
0.000662
GnomAD4 exome
AF:
0.000556
AC:
812
AN:
1461500
Hom.:
3
AF XY:
0.000554
AC XY:
403
AN XY:
727034
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.000468
Gnomad4 NFE exome
AF:
0.000653
Gnomad4 OTH exome
AF:
0.000745
Alfa
AF:
0.000676
Hom.:
0
Bravo
AF:
0.000332
TwinsUK
AF:
0.00108
AC:
4
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000484
AC:
4
ExAC
AF:
0.000910
AC:
110
EpiCase
AF:
0.000382
EpiControl
AF:
0.000178

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeNov 10, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-0.59
Cadd
Benign
9.0
Dann
Benign
0.95
Eigen
Benign
-0.74
Eigen_PC
Benign
-0.84
FATHMM_MKL
Benign
0.048
N
M_CAP
Benign
0.0051
T
MetaRNN
Benign
0.021
T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.31
T
PROVEAN
Uncertain
-2.5
N;N;D
REVEL
Benign
0.017
Sift
Uncertain
0.0050
D;D;D
Sift4G
Uncertain
0.055
T;T;D
Polyphen
0.27
.;B;.
Vest4
0.15
MVP
0.61
MPC
0.15
ClinPred
0.020
T
GERP RS
2.3
Varity_R
0.031
gMVP
0.32

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

LitVar

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

Other links and lift over

dbSNP: rs183383266; hg19: chr2-234217870; COSMIC: COSV101300625; API