22-21642866-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_022044.3(SDF2L1):c.192C>A(p.Ser64Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000188 in 1,594,322 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 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 0 hom. )
Consequence
SDF2L1
NM_022044.3 missense
NM_022044.3 missense
Scores
11
6
2
Clinical Significance
Conservation
PhyloP100: 0.0920
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 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.908
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SDF2L1 | NM_022044.3 | c.192C>A | p.Ser64Arg | missense_variant | 2/3 | ENST00000248958.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SDF2L1 | ENST00000248958.5 | c.192C>A | p.Ser64Arg | missense_variant | 2/3 | 1 | NM_022044.3 | P1 | |
SDF2L1 | ENST00000466935.1 | n.175C>A | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152048Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000163 AC: 34AN: 208550Hom.: 0 AF XY: 0.000148 AC XY: 17AN XY: 114790
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GnomAD4 exome AF: 0.000191 AC: 275AN: 1442274Hom.: 0 Cov.: 32 AF XY: 0.000194 AC XY: 139AN XY: 716218
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GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152048Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7AN XY: 74266
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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 submitter | clinical testing | Ambry Genetics | Apr 17, 2023 | The c.192C>A (p.S64R) alteration is located in exon 2 (coding exon 2) of the SDF2L1 gene. This alteration results from a C to A substitution at nucleotide position 192, causing the serine (S) at amino acid position 64 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of MoRF binding (P = 0.0134);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at