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GeneBe

22-21643951-C-T

Variant summary

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

The NM_022044.3(SDF2L1):c.442C>T(p.Arg148Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,613,924 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

SDF2L1
NM_022044.3 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.74
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29021385).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SDF2L1NM_022044.3 linkuse as main transcriptc.442C>T p.Arg148Cys missense_variant 3/3 ENST00000248958.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SDF2L1ENST00000248958.5 linkuse as main transcriptc.442C>T p.Arg148Cys missense_variant 3/31 NM_022044.3 P1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152146
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:
0.000193
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
GnomAD3 exomes
AF:
0.000104
AC:
26
AN:
250768
Hom.:
0
AF XY:
0.0000885
AC XY:
12
AN XY:
135598
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00120
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000265
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000164
AC:
24
AN:
1461778
Hom.:
0
Cov.:
31
AF XY:
0.0000151
AC XY:
11
AN XY:
727186
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000353
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152146
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000453
ExAC
AF:
0.0000741
AC:
9

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 GeneticsDec 22, 2023The c.442C>T (p.R148C) 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 442, causing the arginine (R) at amino acid position 148 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
Benign
0.18
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.10
Cadd
Pathogenic
27
Dann
Uncertain
1.0
DEOGEN2
Benign
0.40
T
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.95
D
M_CAP
Uncertain
0.15
D
MetaRNN
Benign
0.29
T
MetaSVM
Uncertain
0.25
D
MutationAssessor
Benign
1.3
L
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.60
N
REVEL
Uncertain
0.52
Sift
Benign
0.069
T
Sift4G
Benign
0.078
T
Polyphen
0.98
D
Vest4
0.52
MutPred
0.53
Loss of MoRF binding (P = 0.0718);
MVP
0.99
MPC
1.5
ClinPred
0.22
T
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.38
gMVP
0.74

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: rs141876771; hg19: chr22-21998240; COSMIC: COSV50707939; COSMIC: COSV50707939; API