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GeneBe

22-21642383-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022044.3(SDF2L1):c.47G>A(p.Gly16Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000696 in 1,445,110 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G16R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00073 ( 0 hom. )

Consequence

SDF2L1
NM_022044.3 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0540
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.033517927).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SDF2L1NM_022044.3 linkuse as main transcriptc.47G>A p.Gly16Glu missense_variant 1/3 ENST00000248958.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SDF2L1ENST00000248958.5 linkuse as main transcriptc.47G>A p.Gly16Glu missense_variant 1/31 NM_022044.3 P1
SDF2L1ENST00000466935.1 linkuse as main transcriptn.30G>A non_coding_transcript_exon_variant 1/22

Frequencies

GnomAD3 genomes
AF:
0.000427
AC:
65
AN:
152184
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
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:
0.000867
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000370
AC:
21
AN:
56790
Hom.:
0
AF XY:
0.000244
AC XY:
8
AN XY:
32744
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000969
Gnomad NFE exome
AF:
0.000892
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000728
AC:
941
AN:
1292810
Hom.:
0
Cov.:
31
AF XY:
0.000699
AC XY:
443
AN XY:
633880
show subpopulations
Gnomad4 AFR exome
AF:
0.000123
Gnomad4 AMR exome
AF:
0.0000731
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000115
Gnomad4 NFE exome
AF:
0.000883
Gnomad4 OTH exome
AF:
0.000225
GnomAD4 genome
AF:
0.000427
AC:
65
AN:
152300
Hom.:
0
Cov.:
32
AF XY:
0.000403
AC XY:
30
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.000120
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:
0.000867
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000281
Hom.:
1
Bravo
AF:
0.000431
ExAC
AF:
0.000175
AC:
14

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 GeneticsAug 16, 2021The c.47G>A (p.G16E) alteration is located in exon 1 (coding exon 1) of the SDF2L1 gene. This alteration results from a G to A substitution at nucleotide position 47, causing the glycine (G) at amino acid position 16 to be replaced by a glutamic acid (E). 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
Uncertain
0.36
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.22
Cadd
Benign
17
Dann
Benign
0.88
DEOGEN2
Benign
0.022
T
Eigen
Benign
-0.83
Eigen_PC
Benign
-0.81
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.48
T
M_CAP
Uncertain
0.20
D
MetaRNN
Benign
0.034
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Uncertain
2.1
M
MutationTaster
Benign
0.99
N
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-0.43
N
REVEL
Uncertain
0.41
Sift
Benign
0.43
T
Sift4G
Benign
1.0
T
Polyphen
0.079
B
Vest4
0.41
MVP
0.62
MPC
1.6
ClinPred
0.036
T
GERP RS
1.1
RBP_binding_hub_radar
1.0
RBP_regulation_power_radar
2.1
Varity_R
0.075
gMVP
0.35

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: rs767602490; hg19: chr22-21996672; API