rs1166002350

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr14-30649531-C-A
• chr14-30649531-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.617C>A​(p.Ala206Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,425,002 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SCFD1 NM_016106.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016106.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCFD1	NM_016106.4	MANE Select	c.617C>A	p.Ala206Asp	missense	Exon 8 of 25	NP_057190.2
	SCFD1	NM_001283032.1		c.440C>A	p.Ala147Asp	missense	Exon 7 of 24	NP_001269961.1	Q8WVM8
	SCFD1	NM_182835.2		c.416C>A	p.Ala139Asp	missense	Exon 7 of 24	NP_878255.1	Q8WVM8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCFD1	ENST00000458591.7	TSL:1 MANE Select	c.617C>A	p.Ala206Asp	missense	Exon 8 of 25	ENSP00000390783.2	Q8WVM8-1
	SCFD1	ENST00000555259.5	TSL:1	n.*176C>A		non_coding_transcript_exon	Exon 7 of 18	ENSP00000452323.1	G3V5F3
	SCFD1	ENST00000556768.5	TSL:1	n.*87C>A		non_coding_transcript_exon	Exon 5 of 22	ENSP00000451811.1	G3V4I1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000137 AC: 3 AN: 218694 AF XY: 0.0000252

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000291

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1425002 Hom.: 0 Cov.: 28 AF XY: 0.00000282 AC XY: 2 AN XY: 709160

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 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: 0.00000182 AC: 2 AN: 1097778

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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	0.90	L
PhyloP100		6.9
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.44
Sift	Uncertain	0.017	D
Sift4G	Benign	0.19	T
Polyphen		0.20	B
Vest4		0.88
MutPred		0.42		Gain of solvent accessibility (P = 0.1422)
MVP		0.83
MPC		0.71
ClinPred		0.57	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.43
gMVP		0.82
Mutation Taster		=59/41	polymorphism

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: rs1166002350; hg19: chr14-31118737;