Variant chr1-1223856-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_016176.6(SDF4):c.418C>T(p.Arg140Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000336 in 1,548,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. R140H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000095 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

SDF4
NM_016176.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.828

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDF4	NM_016176.6 linkuse as main transcript	c.418C>T	p.Arg140Cys	missense_variant	3/7	ENST00000360001.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SDF4	ENST00000360001.12 linkuse as main transcript	c.418C>T	p.Arg140Cys	missense_variant	3/7	1	NM_016176.6	P1
SDF4	ENST00000263741.12 linkuse as main transcript	c.418C>T	p.Arg140Cys	missense_variant	3/7	1
SDF4	ENST00000403997.2 linkuse as main transcript	c.244C>T	p.Arg82Cys	missense_variant	2/5	3
SDF4	ENST00000465727.5 linkuse as main transcript	c.439C>T	p.Arg147Cys	missense_variant, NMD_transcript_variant	3/7	2

Frequencies

GnomAD3 genomes

AF:

0.0000949

AC:

AN:

147566

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000681

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000212

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000895

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000534

AC:

AN:

243368

Hom.:

AF XY:

0.0000453

AC XY:

AN XY:

132536

show subpopulations

Gnomad AFR exome

AF:

0.0000623

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000437

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000271

AC:

AN:

1400718

Hom.:

Cov.:

AF XY:

0.0000230

AC XY:

AN XY:

696682

show subpopulations

Gnomad4 AFR exome

AF:

0.0000944

Gnomad4 AMR exome

AF:

0.0000233

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000223

Gnomad4 SAS exome

AF:

0.0000467

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000186

Gnomad4 OTH exome

AF:

0.0000354

GnomAD4 genome

AF:

0.0000949

AC:

AN:

147566

Hom.:

Cov.:

AF XY:

0.0000697

AC XY:

AN XY:

71726

show subpopulations

Gnomad4 AFR

AF:

0.000150

Gnomad4 AMR

AF:

0.0000681

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000212

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000895

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000990

Hom.:

Bravo

AF:

0.000128

ExAC

AF:

0.0000413

AC:

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 submitter

clinical testing

Ambry Genetics

Nov 14, 2023

The c.439C>T (p.R147C) alteration is located in exon 3 (coding exon 2) of the SDF4 gene. This alteration results from a C to T substitution at nucleotide position 439, causing the arginine (R) at amino acid position 147 to be replaced by a cysteine (C). 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

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.68

D;.

Eigen

Benign

0.035

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.97

D;D

M_CAP

Pathogenic

0.32

MetaRNN

Pathogenic

0.83

D;D

MetaSVM

Uncertain

-0.091

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.5

D;D

REVEL

Uncertain

0.43

Sift

Benign

0.20

T;T

Sift4G

Uncertain

0.041

D;D

Polyphen

0.94

P;D

Vest4

0.73

MVP

0.88

MPC

1.1

ClinPred

0.96

GERP RS

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.37

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.

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