Variant chr4-53145578-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152540.4(SCFD2):c.1316T>C(p.Ile439Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000103 in 1,608,062 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

SCFD2
NM_152540.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.62

Variant links:

Genes affected

SCFD2 (HGNC:30676): (sec1 family domain containing 2) Predicted to enable syntaxin binding activity. Predicted to be involved in intracellular protein transport and vesicle docking involved in exocytosis. Predicted to be active in plasma membrane and secretory granule. [provided by Alliance of Genome Resources, Apr 2022]

SCFD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0838013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCFD2	NM_152540.4 linkuse as main transcript	c.1316T>C	p.Ile439Thr	missense_variant	5/9	ENST00000401642.8	NP_689753.2	Q8WU76-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCFD2	ENST00000401642.8 linkuse as main transcript	c.1316T>C	p.Ile439Thr	missense_variant	5/9	1	NM_152540.4	ENSP00000384182.3		Q8WU76-1
SCFD2	ENST00000388940.8 linkuse as main transcript	c.1316T>C	p.Ile439Thr	missense_variant	5/8	2		ENSP00000373592.4		Q8WU76-2

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000110

AC:

AN:

245550

Hom.:

AF XY:

0.000106

AC XY:

AN XY:

132588

show subpopulations

Gnomad AFR exome

AF:

0.000311

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000440

Gnomad SAS exome

AF:

0.0000692

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000981

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.000105

AC:

153

AN:

1455756

Hom.:

Cov.:

AF XY:

0.000104

AC XY:

AN XY:

723862

show subpopulations

Gnomad4 AFR exome

AF:

0.000303

Gnomad4 AMR exome

AF:

0.0000231

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000731

Gnomad4 SAS exome

AF:

0.0000354

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000946

Gnomad4 OTH exome

AF:

0.0000832

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000112

Hom.:

Bravo

AF:

0.000125

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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.1316T>C (p.I439T) alteration is located in exon 5 (coding exon 5) of the SCFD2 gene. This alteration results from a T to C substitution at nucleotide position 1316, causing the isoleucine (I) at amino acid position 439 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

0.10

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.20

T;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.049

MetaRNN

Benign

0.084

T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.4

L;L

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.23

Sift

Benign

0.31

T;T

Sift4G

Uncertain

0.016

D;D

Polyphen

0.0020

B;B

Vest4

0.26

MVP

0.83

MPC

0.45

ClinPred

0.042

GERP RS

4.9

Varity_R

0.083

gMVP

0.25

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