rs146685783

Variant names:

• chr14-30649539-A-G
• rs146685783
• NM_016106.4:c.625A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-30649539-A-G
• chr14-30649539-A-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_016106.4(SCFD1):​c.625A>G​(p.Ile209Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000887 in 1,577,742 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000091 (0 hom.)
• Consequence: SCFD1 NM_016106.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.19
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 13 AD gene.

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.625A>G	p.Ile209Val	missense	Exon 8 of 25	NP_057190.2
	SCFD1	NM_001283032.1		c.448A>G	p.Ile150Val	missense	Exon 7 of 24	NP_001269961.1	Q8WVM8
	SCFD1	NM_182835.2		c.424A>G	p.Ile142Val	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.625A>G	p.Ile209Val	missense	Exon 8 of 25	ENSP00000390783.2	Q8WVM8-1
	SCFD1	ENST00000555259.5	TSL:1	n.*184A>G		non_coding_transcript_exon	Exon 7 of 18	ENSP00000452323.1	G3V5F3
	SCFD1	ENST00000556768.5	TSL:1	n.*95A>G		non_coding_transcript_exon	Exon 5 of 22	ENSP00000451811.1	G3V4I1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000464 AC: 1 AN: 215306 AF XY: 0.00

Gnomad AFR exome AF: 0.0000717

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000912 AC: 13 AN: 1425552 Hom.: 0 Cov.: 28 AF XY: 0.00000705 AC XY: 5 AN XY: 709138

African (AFR) AF: 0.00 AC: 0 AN: 30490

American (AMR) AF: 0.0000285 AC: 1 AN: 35068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25210

East Asian (EAS) AF: 0.00 AC: 0 AN: 37484

South Asian (SAS) AF: 0.00 AC: 0 AN: 80130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.0000109 AC: 12 AN: 1099544

Other (OTH) AF: 0.00 AC: 0 AN: 58814

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74354

African (AFR) AF: 0.0000241 AC: 1 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

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	Benign	0.069
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		8.2
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.18
Sift	Benign	0.076	T
Sift4G	Benign	0.096	T
Polyphen		0.58	P
Vest4		0.61
MVP		0.17
MPC		0.58
ClinPred		0.83	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.40
Mutation Taster		=77/23	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: rs146685783; hg19: chr14-31118745;