rs1216324528

Variant names:

• chr14-30673258-C-G
• rs1216324528
• NM_016106.4:c.997C>G

Your query was ambiguous. Multiple possible variants found:

• chr14-30673258-C-G
• chr14-30673258-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016106.4(SCFD1):​c.997C>G​(p.Pro333Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000141 in 1,420,894 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. 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, splice_region
• Scores: Splicing: ADA: 0.9772
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.88
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

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.997C>G	p.Pro333Ala	missense splice_region	Exon 12 of 25	NP_057190.2
	SCFD1	NM_001283032.1		c.820C>G	p.Pro274Ala	missense splice_region	Exon 11 of 24	NP_001269961.1	Q8WVM8
	SCFD1	NM_182835.2		c.796C>G	p.Pro266Ala	missense splice_region	Exon 11 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.997C>G	p.Pro333Ala	missense splice_region	Exon 12 of 25	ENSP00000390783.2	Q8WVM8-1
	SCFD1	ENST00000555259.5	TSL:1	n.*556C>G		splice_region non_coding_transcript_exon	Exon 11 of 18	ENSP00000452323.1	G3V5F3
	SCFD1	ENST00000556768.5	TSL:1	n.*467C>G		splice_region non_coding_transcript_exon	Exon 9 of 22	ENSP00000451811.1	G3V4I1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000414 AC: 1 AN: 241312 AF XY: 0.00000765

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: 0.00000897

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1420894 Hom.: 0 Cov.: 25 AF XY: 0.00000282 AC XY: 2 AN XY: 708288

African (AFR) AF: 0.00 AC: 0 AN: 32506

American (AMR) AF: 0.00 AC: 0 AN: 41326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25576

East Asian (EAS) AF: 0.00 AC: 0 AN: 38870

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52814

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5660

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1083930

Other (OTH) AF: 0.0000170 AC: 1 AN: 58712

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	Benign	0.32
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.56	D
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		6.9
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.34
Sift	Benign	0.20	T
Sift4G	Benign	0.31	T
Polyphen		0.97	D
Vest4		0.76
MutPred		0.59		Gain of MoRF binding (P = 0.056)
MVP		0.58
MPC		0.96
ClinPred		0.61	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.61
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.98
dbscSNV1_RF	Pathogenic	0.88
SpliceAI score (max)		0.0		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: rs1216324528; hg19: chr14-31142464;