1-1223301-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016176.6(SDF4):​c.499G>A​(p.Glu167Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,708 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SDF4
NM_016176.6 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.91
Variant links:
Genes affected
SDF4 (HGNC:24188): (stromal cell derived factor 4) This gene encodes a stromal cell derived factor that is a member of the CREC protein family. The encoded protein contains six EF-hand motifs and calcium-binding motifs. This protein localizes to the Golgi lumen and may be involved in regulating calcium dependent cellular activities. [provided by RefSeq, Sep 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SDF4NM_016176.6 linkuse as main transcriptc.499G>A p.Glu167Lys missense_variant 4/7 ENST00000360001.12 NP_057260.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SDF4ENST00000360001.12 linkuse as main transcriptc.499G>A p.Glu167Lys missense_variant 4/71 NM_016176.6 ENSP00000353094.7 A0A5F9UP49
SDF4ENST00000263741.12 linkuse as main transcriptc.499G>A p.Glu167Lys missense_variant 4/71 ENSP00000263741.8 A0A5F9UJX7
SDF4ENST00000403997.2 linkuse as main transcriptc.322G>A p.Glu108Lys missense_variant 3/53 ENSP00000384207.2 H0Y3T6
SDF4ENST00000465727.5 linkuse as main transcriptn.520G>A non_coding_transcript_exon_variant 4/72 ENSP00000435962.1 G3V1E2

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251294
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135858
show subpopulations
Gnomad AFR exome
AF:
0.0000615
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461708
Hom.:
0
Cov.:
33
AF XY:
0.00000550
AC XY:
4
AN XY:
727140
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34
Alfa
AF:
0.0000386
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 02, 2024The c.520G>A (p.E174K) alteration is located in exon 4 (coding exon 3) of the SDF4 gene. This alteration results from a G to A substitution at nucleotide position 520, causing the glutamic acid (E) at amino acid position 174 to be replaced by a lysine (K). 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
0.11
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
T;.
Eigen
Benign
0.11
Eigen_PC
Benign
0.030
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.059
D
MetaRNN
Uncertain
0.61
D;D
MetaSVM
Benign
-0.30
T
MutationAssessor
Uncertain
2.3
M;M
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-1.6
N;N
REVEL
Benign
0.28
Sift
Benign
0.23
T;T
Sift4G
Uncertain
0.048
D;T
Polyphen
0.92
P;D
Vest4
0.75
MVP
0.23
MPC
0.70
ClinPred
0.78
D
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.21
gMVP
0.51

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: rs781438857; hg19: chr1-1158681; COSMIC: COSV55418940; COSMIC: COSV55418940; API