rs780100858

Variant names:

• chr14-30643343-C-A
• rs780100858
• NM_016106.4:c.551C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-30643343-C-A
• chr14-30643343-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T184M) has been classified as Uncertain significance.

• 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
• Publications: 0 publications found

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]

ENSG00000301732 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 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

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111458

Other (OTH) AF: 0.00 AC: 0 AN: 60376

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;.;.;.;.;.
PhyloP100		7.1
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
Mutation Taster		=43/57	disease causing

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

Other links and lift over

dbSNP: rs780100858; hg19: chr14-31112549;