dbSNP rs764634276: SDF4:p.Val150Leu (chr1-1223352-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_016176.6(SDF4):c.448G>T(p.Val150Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,898 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: 6.9e-7 ( 0 hom. )

Consequence

SDF4
NM_016176.6 missense

Scores

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]

SDF4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity CAB45_HUMAN

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.448G>T	p.Val150Leu	missense_variant	Exon 4 of 7	ENST00000360001.12	NP_057260.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SDF4	ENST00000360001.12 link	c.448G>T	p.Val150Leu	missense_variant	Exon 4 of 7	1	NM_016176.6	ENSP00000353094.7	A0A5F9UP49
SDF4	ENST00000263741.12 link	c.448G>T	p.Val150Leu	missense_variant	Exon 4 of 7	1		ENSP00000263741.8	A0A5F9UJX7
SDF4	ENST00000403997.2 link	c.271G>T	p.Val91Leu	missense_variant	Exon 3 of 5	3		ENSP00000384207.2	H0Y3T6
SDF4	ENST00000465727.5 link	n.469G>T		non_coding_transcript_exon_variant	Exon 4 of 7	2		ENSP00000435962.1	G3V1E2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455898

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723964

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 10, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.469G>T (p.V157L) alteration is located in exon 4 (coding exon 3) of the SDF4 gene. This alteration results from a G to T substitution at nucleotide position 469, causing the valine (V) at amino acid position 157 to be replaced by a leucine (L). 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

0.60

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.38

T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.16

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.94

D;D

M_CAP

Uncertain

0.17

MetaRNN

Uncertain

0.59

D;D

MetaSVM

Uncertain

-0.17

MutationAssessor

Benign

1.1

L;L

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.6

N;N

REVEL

Uncertain

0.44

Sift

Benign

0.18

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.25

B;B

Vest4

0.82

MutPred

0.52

Loss of disorder (P = 0.2292);Loss of disorder (P = 0.2292);

MVP

0.85

MPC

0.43

ClinPred

0.79

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.50

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over