14-30670296-G-A

Position:

• chr14-30670296-G-A

Variant summary

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

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.33

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 (HGNC:):

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=0.26993033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCFD1	NM_016106.4	c.896G>A	p.Gly299Glu	missense_variant	11/25	ENST00000458591.7	NP_057190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCFD1	ENST00000458591.7	c.896G>A	p.Gly299Glu	missense_variant	11/25	1	NM_016106.4	ENSP00000390783.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444832 Hom.: 0 Cov.: 28 AF XY: 0.00000139 AC XY: 1 AN XY: 718708

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000121

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Mar 19, 2024

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	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.12	T;.;.
Eigen	Benign	-0.076
Eigen_PC	Benign	0.085
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	-0.14	N;.;.
PrimateAI	Uncertain	0.61	T
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	D
GERP RS		4.5
Varity_R		0.10
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-31139502;