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GeneBe

22-21644156-C-T

Variant summary

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

The NM_022044.3(SDF2L1):c.647C>T(p.Ala216Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000502 in 1,613,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00052 ( 0 hom. )

Consequence

SDF2L1
NM_022044.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.999
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=0.019649893).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SDF2L1NM_022044.3 linkuse as main transcriptc.647C>T p.Ala216Val missense_variant 3/3 ENST00000248958.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SDF2L1ENST00000248958.5 linkuse as main transcriptc.647C>T p.Ala216Val missense_variant 3/31 NM_022044.3 P1

Frequencies

GnomAD3 genomes
AF:
0.000322
AC:
49
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000524
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:
0.000529
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.000354
AC:
89
AN:
251192
Hom.:
0
AF XY:
0.000324
AC XY:
44
AN XY:
135752
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000752
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000463
Gnomad NFE exome
AF:
0.000511
Gnomad OTH exome
AF:
0.000490
GnomAD4 exome
AF:
0.000521
AC:
761
AN:
1461786
Hom.:
0
Cov.:
32
AF XY:
0.000491
AC XY:
357
AN XY:
727182
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000738
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000112
Gnomad4 NFE exome
AF:
0.000609
Gnomad4 OTH exome
AF:
0.000712
GnomAD4 genome
AF:
0.000322
AC:
49
AN:
152172
Hom.:
0
Cov.:
32
AF XY:
0.000350
AC XY:
26
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.000524
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000529
Gnomad4 OTH
AF:
0.00144
Alfa
AF:
0.000489
Hom.:
0
Bravo
AF:
0.000370
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000778
AC:
3
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000930
AC:
8
ExAC
AF:
0.000329
AC:
40
EpiCase
AF:
0.000654
EpiControl
AF:
0.00113

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 GeneticsMay 01, 2023The c.647C>T (p.A216V) 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 647, causing the alanine (A) at amino acid position 216 to be replaced by a valine (V). 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
0.076
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.45
Cadd
Benign
16
Dann
Uncertain
0.98
DEOGEN2
Benign
0.016
T
Eigen
Benign
-0.99
Eigen_PC
Benign
-0.93
FATHMM_MKL
Benign
0.71
D
LIST_S2
Benign
0.70
T
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.020
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.67
N
MutationTaster
Benign
0.99
N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.44
N
REVEL
Benign
0.17
Sift
Benign
0.33
T
Sift4G
Benign
0.43
T
Polyphen
0.0
B
Vest4
0.073
MVP
0.55
MPC
0.52
ClinPred
0.026
T
GERP RS
0.17
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.11
gMVP
0.52

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: rs144265283; hg19: chr22-21998445; API