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GeneBe

22-21643990-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_022044.3(SDF2L1):c.481C>T(p.Arg161Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,614,136 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: 0.000017 ( 0 hom. )

Consequence

SDF2L1
NM_022044.3 missense

Scores

15
2
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.907

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SDF2L1NM_022044.3 linkuse as main transcriptc.481C>T p.Arg161Cys missense_variant 3/3 ENST00000248958.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SDF2L1ENST00000248958.5 linkuse as main transcriptc.481C>T p.Arg161Cys missense_variant 3/31 NM_022044.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152176
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
251088
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135782
show subpopulations
Gnomad AFR exome
AF:
0.000246
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000171
AC:
25
AN:
1461842
Hom.:
0
Cov.:
31
AF XY:
0.0000165
AC XY:
12
AN XY:
727214
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152294
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000378
ExAC
AF:
0.0000165
AC:
2

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 29, 2024The c.481C>T (p.R161C) 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 481, causing the arginine (R) at amino acid position 161 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
0.31
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.43
Cadd
Pathogenic
34
Dann
Pathogenic
1.0
DEOGEN2
Pathogenic
0.86
D
Eigen
Pathogenic
0.93
Eigen_PC
Pathogenic
0.81
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.97
D
M_CAP
Pathogenic
0.36
D
MetaRNN
Pathogenic
0.91
D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Pathogenic
4.0
H
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.65
T
PROVEAN
Pathogenic
-6.3
D
REVEL
Pathogenic
0.92
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.93
MutPred
0.66
Loss of methylation at R161 (P = 0.0371);
MVP
0.99
MPC
1.7
ClinPred
1.0
D
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.89
gMVP
0.88

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: rs555950380; hg19: chr22-21998279; API