Genetic Variant SDF4:p.Ter342Argext*? (chr1-1217672-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016176.6(SDF4):c.908T>C(p.Met303Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,582 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SDF4
NM_016176.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.19

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26328355).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDF4	NM_016176.6 link	c.908T>C	p.Met303Thr	missense_variant	Exon 7 of 7	ENST00000360001.12	NP_057260.3
SDF4	NM_016547.3 link	c.1024T>C	p.Ter342Argext*?	stop_lost	Exon 7 of 7		NP_057631.2	Q9BRK5A0A024R0A9
SDF4	XM_047422112.1 link	c.1045T>C	p.Ter349Argext*?	stop_lost	Exon 7 of 7		XP_047278068.1
SDF4	XM_047422111.1 link	c.929T>C	p.Met310Thr	missense_variant	Exon 7 of 7		XP_047278067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDF4	ENST00000360001.12 link	c.908T>C	p.Met303Thr	missense_variant	Exon 7 of 7	1	NM_016176.6	ENSP00000353094.7		A0A5F9UP49

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461582

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727084

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.0000224

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53224

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111938

Other (OTH)

AF:

0.00

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 08, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.929T>C (p.M310T) alteration is located in exon 7 (coding exon 6) of the SDF4 gene. This alteration results from a T to C substitution at nucleotide position 929, causing the methionine (M) at amino acid position 310 to be replaced by a threonine (T). 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

0.19

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.79

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.49

PhyloP100

7.2

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.98

REVEL

Benign

0.21

Sift

Benign

0.10

Sift4G

Benign

0.073

Polyphen

0.033

Vest4

0.50

MutPred

0.29

Gain of glycosylation at M310 (P = 0.0472);

MVP

0.20

MPC

0.43

ClinPred

0.90

GERP RS

5.3

Varity_R

0.27

gMVP

0.71

Mutation Taster

=59/141

disease causing

(source)

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

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1-1217672-A-G

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