chr14-30643343-C-A

Variant names:

• chr14-30643343-C-A
• NM_016106.4:c.551C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016106.4(SCFD1):​c.551C>A​(p.Thr184Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,180 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SCFD1 NM_016106.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.07

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCFD1	NM_016106.4	c.551C>A	p.Thr184Lys	missense_variant	Exon 7 of 25	ENST00000458591.7	NP_057190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCFD1	ENST00000458591.7	c.551C>A	p.Thr184Lys	missense_variant	Exon 7 of 25	1	NM_016106.4	ENSP00000390783.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461180 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726882

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

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	Benign	0.31
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.46	T;.;T;.;.;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D;D;D;D;D
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.61	D;D;D;D;D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.1	L;.;.;.;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.8	D;D;D;D;D;D
REVEL	Uncertain	0.50
Sift	Benign	0.31	T;T;T;T;T;T
Sift4G	Benign	0.76	T;T;T;T;T;T
Polyphen		0.79	P;.;.;.;.;.
Vest4		0.77
MutPred		0.46		Gain of ubiquitination at T184 (P = 0.0185);.;.;.;.;.;
MVP		0.81
MPC		0.83
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.45
gMVP		0.65

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: chr14-31112549;