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GeneBe

22-21644056-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_022044.3(SDF2L1):c.547C>T(p.Arg183Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SDF2L1
NM_022044.3 missense

Scores

5
11
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.816

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SDF2L1NM_022044.3 linkuse as main transcriptc.547C>T p.Arg183Cys missense_variant 3/3 ENST00000248958.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SDF2L1ENST00000248958.5 linkuse as main transcriptc.547C>T p.Arg183Cys missense_variant 3/31 NM_022044.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152156
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461882
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152156
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000227

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 06, 2023The c.547C>T (p.R183C) alteration is located in exon 3 (coding exon 3) of the SDF2L1 gene. This alteration results from a C to T substitution at nucleotide position 547, causing the arginine (R) at amino acid position 183 to be replaced by a cysteine (C). 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
0.35
BayesDel_addAF
Pathogenic
0.31
D
BayesDel_noAF
Pathogenic
0.20
Cadd
Pathogenic
32
Dann
Pathogenic
1.0
DEOGEN2
Benign
0.19
T
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.82
D
MetaSVM
Uncertain
0.37
D
MutationAssessor
Uncertain
2.1
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.50
T
PROVEAN
Uncertain
-3.7
D
REVEL
Uncertain
0.63
Sift
Uncertain
0.026
D
Sift4G
Benign
0.069
T
Polyphen
1.0
D
Vest4
0.72
MVP
0.95
MPC
1.7
ClinPred
1.0
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.41
gMVP
0.73

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: rs1454973895; hg19: chr22-21998345; COSMIC: COSV50708085; COSMIC: COSV50708085; API