Genetic Variant SDF4:p.Arg196Ser (chr1-1218898-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016176.6(SDF4):c.586C>A(p.Arg196Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,447,722 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R196C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SDF4
NM_016176.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.61

Publications

0 publications found

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]

SDF4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDF4	NM_016176.6 link	c.586C>A	p.Arg196Ser	missense_variant	Exon 5 of 7	ENST00000360001.12	NP_057260.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDF4	ENST00000360001.12 link	c.586C>A	p.Arg196Ser	missense_variant	Exon 5 of 7	1	NM_016176.6	ENSP00000353094.7		A0A5F9UP49

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000414

AC:

AN:

1447722

Hom.:

Cov.:

AF XY:

0.00000418

AC XY:

AN XY:

718136

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33220

American (AMR)

AF:

0.00

AC:

AN:

43882

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25384

East Asian (EAS)

AF:

0.00

AC:

AN:

39444

South Asian (SAS)

AF:

0.00

AC:

AN:

85006

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52216

Middle Eastern (MID)

AF:

0.000349

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.00000272

AC:

AN:

1103148

Other (OTH)

AF:

0.0000168

AC:

AN:

59696

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 07, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.607C>A (p.R203S) alteration is located in exon 5 (coding exon 4) of the SDF4 gene. This alteration results from a C to A substitution at nucleotide position 607, causing the arginine (R) at amino acid position 203 to be replaced by a serine (S). 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

Pathogenic

0.96

BayesDel_addAF

Uncertain

0.094

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.62

D;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.72

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;M

PhyloP100

9.6

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-3.5

D;D

REVEL

Uncertain

0.46

Sift

Benign

0.068

T;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.48

P;D

Vest4

0.92

MutPred

0.69

Gain of disorder (P = 0.0674);Gain of disorder (P = 0.0674);

MVP

0.26

MPC

1.2

ClinPred

0.97

GERP RS

4.7

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.0

Varity_R

0.56

gMVP

0.87

Mutation Taster

=14/86

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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1-1218898-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over