Variant chr1-1217591-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016176.6(SDF4):c.989A>G(p.Glu330Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000923 in 1,613,622 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: 𝑓 0.00048 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

SDF4
NM_016176.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.68

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.025177926).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SDF4	NM_016176.6 linkuse as main transcript	c.989A>G	p.Glu330Gly	missense_variant	7/7	ENST00000360001.12
SDF4	XM_047422111.1 linkuse as main transcript	c.1010A>G	p.Glu337Gly	missense_variant	7/7
SDF4	NM_016547.3 linkuse as main transcript	c.*79A>G		3_prime_UTR_variant	7/7
SDF4	XM_047422112.1 linkuse as main transcript	c.*79A>G		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDF4	ENST00000360001.12 linkuse as main transcript	c.989A>G	p.Glu330Gly	missense_variant	7/7	1	NM_016176.6	P1

Frequencies

GnomAD3 genomes

AF:

0.000487

AC:

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000168

AC:

AN:

250564

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.00241

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000520

AC:

AN:

1461468

Hom.:

Cov.:

AF XY:

0.0000454

AC XY:

AN XY:

727018

show subpopulations

Gnomad4 AFR exome

AF:

0.00194

Gnomad4 AMR exome

AF:

0.0000671

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:

0.00000180

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.000480

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000194

Hom.:

Bravo

AF:

0.000740

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000214

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

Mar 19, 2024

The c.1010A>G (p.E337G) alteration is located in exon 7 (coding exon 6) of the SDF4 gene. This alteration results from a A to G substitution at nucleotide position 1010, causing the glutamic acid (E) at amino acid position 337 to be replaced by a glycine (G). 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

0.16

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.58

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

M_CAP

Uncertain

0.095

MetaRNN

Benign

0.025

MetaSVM

Benign

-0.66

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.3

REVEL

Benign

0.29

Sift

Benign

0.20

Sift4G

Uncertain

0.016

Polyphen

0.41

Vest4

0.48

MVP

0.72

MPC

0.55

ClinPred

0.050

GERP RS

5.3

Varity_R

0.11

gMVP

0.67

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