Genetic Variant SCFD1:p.Gly299Glu (chr14-30670296-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_016106.4(SCFD1):c.896G>A(p.Gly299Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,444,832 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: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SCFD1
NM_016106.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.33

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26993033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCFD1	NM_016106.4 link	c.896G>A	p.Gly299Glu	missense_variant	Exon 11 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.896G>A	p.Gly299Glu	missense_variant	Exon 11 of 25	1	NM_016106.4	ENSP00000390783.2		Q8WVM8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1444832

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718708

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32370

American (AMR)

AF:

0.00

AC:

AN:

40892

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25764

East Asian (EAS)

AF:

0.00

AC:

AN:

39238

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82564

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5476

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105448

Other (OTH)

AF:

0.00

AC:

AN:

59756

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 19, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.896G>A (p.G299E) alteration is located in exon 11 (coding exon 11) of the SCFD1 gene. This alteration results from a G to A substitution at nucleotide position 896, causing the glycine (G) at amino acid position 299 to be replaced by a glutamic acid (E). 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

0.22

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.12

T;.;.

Eigen

Benign

-0.076

Eigen_PC

Benign

0.085

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.036

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

-0.14

N;.;.

PhyloP100

4.3

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.0

N;N;N

REVEL

Uncertain

0.29

Sift

Benign

0.12

T;T;T

Sift4G

Benign

0.38

T;T;T

Polyphen

0.0040

B;.;.

Vest4

0.42

MutPred

0.43

Gain of loop (P = 0.0312);.;.;

MVP

0.91

MPC

0.47

ClinPred

0.67

GERP RS

4.5

Varity_R

0.10

gMVP

0.59

Mutation Taster

=44/56

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over