14-30649539-A-T

Variant names:

• chr14-30649539-A-T
• NM_016106.4:c.625A>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016106.4(SCFD1):​c.625A>T​(p.Ile209Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,425,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SCFD1 NM_016106.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.19

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.79

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCFD1	NM_016106.4	c.625A>T	p.Ile209Leu	missense_variant	Exon 8 of 25	ENST00000458591.7	NP_057190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCFD1	ENST00000458591.7	c.625A>T	p.Ile209Leu	missense_variant	Exon 8 of 25	1	NM_016106.4	ENSP00000390783.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1425552 Hom.: 0 Cov.: 28 AF XY: 0.00000141 AC XY: 1 AN XY: 709138

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: 0.0000125

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T;.;T;.;.;T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;D
M_CAP	Benign	0.057	D
MetaRNN	Pathogenic	0.79	D;D;D;D;D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Pathogenic	3.1	M;.;.;.;.;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.8	N;N;N;N;N;N
REVEL	Uncertain	0.34
Sift	Uncertain	0.0040	D;D;D;D;D;D
Sift4G	Uncertain	0.013	D;D;D;D;D;D
Polyphen		0.98	D;.;.;.;.;.
Vest4		0.76
MutPred		0.80		Gain of methylation at R214 (P = 0.2066);.;.;.;.;.;
MVP		0.35
MPC		1.1
ClinPred		0.98	D
GERP RS		5.4
Varity_R		0.48
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.33		Position offset: 8

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: chr14-31118745;