Variant chr14-30630553-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_016106.4(SCFD1):c.209T>C(p.Ile70Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00323 in 1,573,924 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0032 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 17 hom. )

Consequence

SCFD1
NM_016106.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 7.56

Variant links:

Genes affected

SCFD1 (HGNC:20726): (sec1 family domain containing 1) Predicted to enable syntaxin binding activity. Involved in negative regulation of autophagosome assembly; regulation of protein transport; and response to toxic substance. Located in cis-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

SCFD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020704448).

BP6

Variant 14-30630553-T-C is Benign according to our data. Variant chr14-30630553-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 976653.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS2

High AC in GnomAd4 at 493 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCFD1	NM_016106.4 linkuse as main transcript	c.209T>C	p.Ile70Thr	missense_variant	3/25	ENST00000458591.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCFD1	ENST00000458591.7 linkuse as main transcript	c.209T>C	p.Ile70Thr	missense_variant	3/25	1	NM_016106.4	A2	Q8WVM8-1

Frequencies

GnomAD3 genomes

AF:

0.00324

AC:

493

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00825

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00349

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00418

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00330

AC:

827

AN:

250812

Hom.:

AF XY:

0.00334

AC XY:

453

AN XY:

135580

show subpopulations

Gnomad AFR exome

AF:

0.000616

Gnomad AMR exome

AF:

0.00492

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00216

Gnomad FIN exome

AF:

0.00403

Gnomad NFE exome

AF:

0.00411

Gnomad OTH exome

AF:

0.00409

GnomAD4 exome

AF:

0.00322

AC:

4584

AN:

1421620

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

2301

AN XY:

709872

show subpopulations

Gnomad4 AFR exome

AF:

0.000533

Gnomad4 AMR exome

AF:

0.00499

Gnomad4 ASJ exome

AF:

0.000426

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00204

Gnomad4 FIN exome

AF:

0.00443

Gnomad4 NFE exome

AF:

0.00348

Gnomad4 OTH exome

AF:

0.00290

GnomAD4 genome

AF:

0.00324

AC:

493

AN:

152304

Hom.:

Cov.:

AF XY:

0.00320

AC XY:

238

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000625

Gnomad4 AMR

AF:

0.00824

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00349

Gnomad4 NFE

AF:

0.00418

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00360

Hom.:

Bravo

AF:

0.00349

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00523

AC:

ExAC

AF:

0.00329

AC:

399

Asia WGS

AF:

0.000868

AC:

AN:

3472

EpiCase

AF:

0.00294

EpiControl

AF:

0.00279

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Amyotrophic lateral sclerosis

Uncertain:1

Uncertain significance, criteria provided, single submitter

case-control

UM ALS/MND Lab, University Of Malta

Jul 31, 2020

Frequency of the Ile70Thr variant in the SCFD1 gene is slightly higher for ALS patients (0.004660) compared to controls (0.003843) within the Project MinE ALS case-control cohort. In this context, since the evidence is not strong enough to support causation or genetic risk, the variant has been classified as having uncertain significance. -

SCFD1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 21, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Uncertain

0.082

BayesDel_noAF

Pathogenic

0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.79

D;.;D

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.021

T;T;T

MetaSVM

Uncertain

0.36

MutationAssessor

Benign

1.8

L;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Pathogenic

0.86

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.35

B;.;.

Vest4

0.90

MVP

0.92

MPC

1.1

ClinPred

0.028

GERP RS

5.6

Varity_R

0.54

gMVP

0.77

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