14-30630553-T-C

Variant names:

• chr14-30630553-T-C
• rs61754480
• NM_016106.4:c.209T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_016106.4(SCFD1):​c.209T>C​(p.Ile70Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00323 in 1,573,924 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (17 hom.)
• Consequence: SCFD1 NM_016106.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2 B:1
• Conservation: PhyloP100: 7.56
• Publications: 13 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.020704448).
• BS2: High AC in GnomAd4 at 493 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.209T>C	p.Ile70Thr	missense	Exon 3 of 25	NP_057190.2
	SCFD1	NM_182835.2		c.8T>C	p.Ile3Thr	missense	Exon 2 of 24	NP_878255.1	Q8WVM8-3
	SCFD1	NM_001283031.1		c.-259T>C		5_prime_UTR	Exon 3 of 24	NP_001269960.1	B7Z5N7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCFD1	ENST00000458591.7	TSL:1 MANE Select	c.209T>C	p.Ile70Thr	missense	Exon 3 of 25	ENSP00000390783.2	Q8WVM8-1
	SCFD1	ENST00000555259.5	TSL:1	n.209T>C		non_coding_transcript_exon	Exon 3 of 18	ENSP00000452323.1	G3V5F3
	SCFD1	ENST00000556768.5	TSL:1	n.209T>C		non_coding_transcript_exon	Exon 3 of 22	ENSP00000451811.1	G3V4I1

Frequencies

GnomAD3 genomes AF: 0.00324 AC: 493 AN: 152186 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00825

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00349

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00418

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00330 AC: 827 AN: 250812 AF XY: 0.00334

Gnomad AFR exome AF: 0.000616

Gnomad AMR exome AF: 0.00492

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00403

Gnomad NFE exome AF: 0.00411

Gnomad OTH exome AF: 0.00409

GnomAD4 exome AF: 0.00322 AC: 4584 AN: 1421620 Hom.: 17 Cov.: 25 AF XY: 0.00324 AC XY: 2301 AN XY: 709872

African (AFR) AF: 0.000533 AC: 17 AN: 31880

American (AMR) AF: 0.00499 AC: 222 AN: 44502

Ashkenazi Jewish (ASJ) AF: 0.000426 AC: 11 AN: 25838

East Asian (EAS) AF: 0.00 AC: 0 AN: 39230

South Asian (SAS) AF: 0.00204 AC: 174 AN: 85320

European-Finnish (FIN) AF: 0.00443 AC: 236 AN: 53322

Middle Eastern (MID) AF: 0.00176 AC: 10 AN: 5678

European-Non Finnish (NFE) AF: 0.00348 AC: 3743 AN: 1076936

Other (OTH) AF: 0.00290 AC: 171 AN: 58914

GnomAD4 genome AF: 0.00324 AC: 493 AN: 152304 Hom.: 2 Cov.: 32 AF XY: 0.00320 AC XY: 238 AN XY: 74468

African (AFR) AF: 0.000625 AC: 26 AN: 41578

American (AMR) AF: 0.00824 AC: 126 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4832

European-Finnish (FIN) AF: 0.00349 AC: 37 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00418 AC: 284 AN: 68004

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00348 Hom.: 5

Bravo AF: 0.00349

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00467 AC: 18

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00523 AC: 45

ExAC AF: 0.00329 AC: 399

Asia WGS AF: 0.000868 AC: 3 AN: 3472

EpiCase AF: 0.00294

EpiControl AF: 0.00279

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Amyotrophic lateral sclerosis (1)
-	1	-	not provided (1)
-	-	1	SCFD1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Pathogenic	0.35
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.79	D
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.021	T
MetaSVM	Uncertain	0.36	D
MutationAssessor	Benign	1.8	L
PhyloP100		7.6
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.4	D
REVEL	Pathogenic	0.86
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.35	B
Vest4		0.90
MVP		0.92
MPC		1.1
ClinPred		0.028	T
GERP RS		5.6
Varity_R		0.54
gMVP		0.77
Mutation Taster		=44/56	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs61754480; hg19: chr14-31099759;