14-30702330-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016106.4(SCFD1):c.1445A>G(p.Asp482Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: SCFD1 NM_016106.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.40

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27553666).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCFD1	NM_016106.4	c.1445A>G	p.Asp482Gly	missense_variant	17/25	ENST00000458591.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCFD1	ENST00000458591.7	c.1445A>G	p.Asp482Gly	missense_variant	17/25	1	NM_016106.4	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.1445A>G (p.D482G) alteration is located in exon 17 (coding exon 17) of the SCFD1 gene. This alteration results from a A to G substitution at nucleotide position 1445, causing the aspartic acid (D) at amino acid position 482 to be replaced by a glycine (G). 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	0.17
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
Cadd	Uncertain	23
Dann	Benign	0.97
DEOGEN2	Benign	0.27	T;.;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.094
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.1	L;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.97	N;N;N
REVEL	Uncertain	0.45
Sift	Benign	0.13	T;T;T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.0010	B;.;.
Vest4		0.47
MutPred		0.48		Gain of ubiquitination at K477 (P = 0.1008);.;.;
MVP		0.98
MPC		0.47
ClinPred		0.91	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.55

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

Other links and lift over

dbSNP: rs1891136381; hg19: chr14-31171536;