Variant chr1-1223292-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_016176.6(SDF4):c.508G>A(p.Val170Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000335 in 1,614,016 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00034 ( 2 hom. )

Consequence

SDF4
NM_016176.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0620

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015903354).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDF4	NM_016176.6 linkuse as main transcript	c.508G>A	p.Val170Ile	missense_variant	4/7	ENST00000360001.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SDF4	ENST00000360001.12 linkuse as main transcript	c.508G>A	p.Val170Ile	missense_variant	4/7	1	NM_016176.6	P1
SDF4	ENST00000263741.12 linkuse as main transcript	c.508G>A	p.Val170Ile	missense_variant	4/7	1
SDF4	ENST00000403997.2 linkuse as main transcript	c.334G>A	p.Val112Ile	missense_variant	3/5	3
SDF4	ENST00000465727.5 linkuse as main transcript	c.529G>A	p.Val177Ile	missense_variant, NMD_transcript_variant	4/7	2

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152270

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

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:

0.000353

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000159

AC:

AN:

251322

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000174

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:

0.000290

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000339

AC:

495

AN:

1461746

Hom.:

Cov.:

AF XY:

0.000330

AC XY:

240

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000134

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:

0.000433

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000296

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000320

Hom.:

Bravo

AF:

0.000310

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000415

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

Dec 07, 2021

The c.529G>A (p.V177I) alteration is located in exon 4 (coding exon 3) of the SDF4 gene. This alteration results from a G to A substitution at nucleotide position 529, causing the valine (V) at amino acid position 177 to be replaced by an isoleucine (I). 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

0.085

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.1

DANN

Benign

0.70

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.016

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.11

N;N

MutationTaster

Benign

0.94

D;D;D

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.010

N;N

REVEL

Benign

0.0060

Sift

Benign

0.94

T;T

Sift4G

Benign

0.81

T;T

Polyphen

0.0

B;B

Vest4

0.12

MVP

0.072

MPC

0.29

ClinPred

0.0078

GERP RS

-0.023

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.014

gMVP

0.13

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