Genetic Variant SCFD1:p.Asp158Asn (chr14-30639813-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_016106.4(SCFD1):c.472G>A(p.Asp158Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000576 in 1,580,218 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000033 ( 1 hom. )

Consequence

SCFD1
NM_016106.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.23

Publications

0 publications found

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:

ENSG00000301732 (HGNC:):

ENSG00000301732 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 44 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCFD1	NM_016106.4 link	c.472G>A	p.Asp158Asn	missense_variant	Exon 6 of 25	ENST00000458591.7	NP_057190.2	Q8WVM8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCFD1	ENST00000458591.7 link	c.472G>A	p.Asp158Asn	missense_variant	Exon 6 of 25	1	NM_016106.4	ENSP00000390783.2		Q8WVM8-1

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000513

AC:

AN:

233824

AF XY:

0.0000316

show subpopulations

Gnomad AFR exome

AF:

0.000582

Gnomad AMR exome

AF:

0.0000346

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000329

AC:

AN:

1428012

Hom.:

Cov.:

AF XY:

0.0000338

AC XY:

AN XY:

709640

show subpopulations

African (AFR)

AF:

0.000691

AC:

AN:

31858

American (AMR)

AF:

0.0000256

AC:

AN:

39096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25080

East Asian (EAS)

AF:

0.00

AC:

AN:

38674

South Asian (SAS)

AF:

0.0000611

AC:

AN:

81882

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51306

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5556

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1095824

Other (OTH)

AF:

0.000323

AC:

AN:

58736

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.404

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000289

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.00104

AC:

AN:

41530

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000317

ESP6500AA

AF:

0.000457

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 11, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.472G>A (p.D158N) alteration is located in exon 6 (coding exon 6) of the SCFD1 gene. This alteration results from a G to A substitution at nucleotide position 472, causing the aspartic acid (D) at amino acid position 158 to be replaced by an asparagine (N). 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

0.15

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.51

D;.;D;.;D

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D;D;D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.092

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.;.;.;.

PhyloP100

7.2

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-3.0

D;D;D;D;D

REVEL

Benign

0.13

Sift

Benign

0.12

T;T;T;T;T

Sift4G

Benign

0.25

T;T;T;T;T

Polyphen

0.43

B;.;.;.;.

Vest4

0.48

MVP

0.39

MPC

0.76

ClinPred

0.13

GERP RS

5.9

Varity_R

0.30

gMVP

0.51

Mutation Taster

=16/84

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.23

Position offset: -36

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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14-30639813-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over