14-30649531-C-T

Variant names:

• chr14-30649531-C-T
• rs1166002350
• NM_016106.4:c.617C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016106.4(SCFD1):​c.617C>T​(p.Ala206Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000702 in 1,425,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. A206D) has been classified as Uncertain significance.

• 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: 6.95
• 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.617C>T	p.Ala206Val	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.617C>T	p.Ala206Val	missense_variant	Exon 8 of 25	1	NM_016106.4	ENSP00000390783.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1425002 Hom.: 0 Cov.: 28 AF XY: 0.00000141 AC XY: 1 AN XY: 709160

African (AFR) AF: 0.00 AC: 0 AN: 30594

American (AMR) AF: 0.00 AC: 0 AN: 35788

Ashkenazi Jewish (ASJ) AF: 0.0000395 AC: 1 AN: 25298

East Asian (EAS) AF: 0.00 AC: 0 AN: 37504

South Asian (SAS) AF: 0.00 AC: 0 AN: 80398

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097778

Other (OTH) AF: 0.00 AC: 0 AN: 58828

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Benign	0.45
DEOGEN2	Benign	0.11	T;.;T;.;.;T
Eigen	Benign	-0.21
Eigen_PC	Benign	0.062
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.97	D;D;D;D;D;D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.25	T;T;T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	-0.71	N;.;.;.;.;.
PhyloP100		6.9
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	0.30	N;N;N;N;N;N
REVEL	Uncertain	0.33
Sift	Benign	0.68	T;T;T;T;T;T
Sift4G	Benign	0.59	T;T;T;D;T;T
Polyphen		0.0080	B;.;.;.;.;.
Vest4		0.74
MutPred		0.47		Loss of sheet (P = 0.302);.;.;.;.;.;
MVP		0.59
MPC		0.36
ClinPred		0.93	D
GERP RS		5.4
Varity_R		0.16
gMVP		0.58
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.30		Position offset: 16

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1166002350; hg19: chr14-31118737; COSMIC: COSV61724874; COSMIC: COSV61724874;