Menu
GeneBe

22-21643913-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_022044.3(SDF2L1):c.404A>G(p.Glu135Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,612,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

SDF2L1
NM_022044.3 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.94
Variant links:
Genes affected
SDF2L1 (HGNC:10676): (stromal cell derived factor 2 like 1) Enables misfolded protein binding activity. Involved in chaperone cofactor-dependent protein refolding. Located in endoplasmic reticulum. Part of chaperone complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3201576).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SDF2L1NM_022044.3 linkuse as main transcriptc.404A>G p.Glu135Gly missense_variant 3/3 ENST00000248958.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SDF2L1ENST00000248958.5 linkuse as main transcriptc.404A>G p.Glu135Gly missense_variant 3/31 NM_022044.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
151878
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000883
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000521
AC:
13
AN:
249356
Hom.:
0
AF XY:
0.0000742
AC XY:
10
AN XY:
134782
show subpopulations
Gnomad AFR exome
AF:
0.0000617
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000890
Gnomad OTH exome
AF:
0.000328
GnomAD4 exome
AF:
0.0000404
AC:
59
AN:
1460894
Hom.:
0
Cov.:
31
AF XY:
0.0000399
AC XY:
29
AN XY:
726560
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000504
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000395
AC:
6
AN:
151878
Hom.:
0
Cov.:
32
AF XY:
0.0000270
AC XY:
2
AN XY:
74180
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000883
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000403
Hom.:
0
Bravo
AF:
0.0000340
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

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 submitterclinical testingAmbry GeneticsJan 12, 2024The c.404A>G (p.E135G) alteration is located in exon 3 (coding exon 3) of the SDF2L1 gene. This alteration results from a A to G substitution at nucleotide position 404, causing the glutamic acid (E) at amino acid position 135 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.069
T
BayesDel_noAF
Benign
-0.14
Cadd
Pathogenic
27
Dann
Uncertain
0.99
DEOGEN2
Uncertain
0.47
T
Eigen
Benign
-0.070
Eigen_PC
Benign
0.089
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.91
D
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.32
T
MetaSVM
Benign
-0.35
T
MutationAssessor
Benign
1.4
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.50
T
PROVEAN
Pathogenic
-4.5
D
REVEL
Uncertain
0.38
Sift
Benign
0.081
T
Sift4G
Benign
0.16
T
Polyphen
0.011
B
Vest4
0.28
MVP
0.96
MPC
1.2
ClinPred
0.48
T
GERP RS
4.3
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.0
Varity_R
0.30
gMVP
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs370702646; hg19: chr22-21998202; API