4-52885859-C-T

Variant names:

• chr4-52885859-C-T
• rs141706393
• NM_152540.4:c.1850G>A

Variant summary

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

The NM_152540.4(SCFD2):​c.1850G>A​(p.Arg617Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000242 in 1,613,996 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R617L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: SCFD2 NM_152540.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.56
• Publications: 8 publications found

Genes affected

SCFD2 (HGNC:30676): (sec1 family domain containing 2) Predicted to enable syntaxin binding activity. Predicted to be involved in intracellular protein transport and vesicle docking involved in exocytosis. Predicted to be active in plasma membrane and secretory granule. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152540.4. 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
	SCFD2	NM_152540.4	MANE Select	c.1850G>A	p.Arg617Gln	missense	Exon 8 of 9	NP_689753.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCFD2	ENST00000401642.8	TSL:1 MANE Select	c.1850G>A	p.Arg617Gln	missense	Exon 8 of 9	ENSP00000384182.3	Q8WU76-1
	SCFD2	ENST00000910196.1		c.1883G>A	p.Arg628Gln	missense	Exon 9 of 10	ENSP00000580255.1
	SCFD2	ENST00000388940.8	TSL:2	c.1715G>A	p.Arg572Gln	missense	Exon 7 of 8	ENSP00000373592.4	Q8WU76-2

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000796 AC: 20 AN: 251372 AF XY: 0.0000810

Gnomad AFR exome AF: 0.0000615

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: 0.000114

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000253 AC: 370 AN: 1461730 Hom.: 0 Cov.: 31 AF XY: 0.000263 AC XY: 191 AN XY: 727162

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39690

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

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

European-Non Finnish (NFE) AF: 0.000311 AC: 346 AN: 1111896

Other (OTH) AF: 0.000215 AC: 13 AN: 60392

GnomAD4 genome AF: 0.000131 AC: 20 AN: 152266 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74448

African (AFR) AF: 0.000120 AC: 5 AN: 41542

American (AMR) AF: 0.0000654 AC: 1 AN: 15298

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000250 Hom.: 0

Bravo AF: 0.000140

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.000164

EpiControl AF: 0.000178

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	0.29
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.094	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Uncertain	0.27	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.6
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.34
Sift	Benign	0.059	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.52
MVP		0.85
MPC		0.66
ClinPred		0.30	T
GERP RS		5.1
Varity_R		0.16
gMVP		0.50
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs141706393; hg19: chr4-53752026; COSMIC: COSV66370419;