14-30639852-G-A

Variant names:

• chr14-30639852-G-A
• rs376363317
• NM_016106.4:c.511G>A

Variant summary

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

The NM_016106.4(SCFD1):​c.511G>A​(p.Val171Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000879 in 1,581,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000093 (0 hom.)
• Consequence: SCFD1 NM_016106.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.67
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05306089).
• BS2: High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCFD1	NM_016106.4	c.511G>A	p.Val171Ile	missense_variant	Exon 6 of 25	ENST00000458591.7	NP_057190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCFD1	ENST00000458591.7	c.511G>A	p.Val171Ile	missense_variant	Exon 6 of 25	1	NM_016106.4	ENSP00000390783.2

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 152058 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000127 AC: 3 AN: 236130 AF XY: 0.00000781

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: 0.0000274

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000930 AC: 133 AN: 1429356 Hom.: 0 Cov.: 30 AF XY: 0.0000845 AC XY: 60 AN XY: 710270

African (AFR) AF: 0.00 AC: 0 AN: 32020

American (AMR) AF: 0.00 AC: 0 AN: 39726

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25158

East Asian (EAS) AF: 0.00 AC: 0 AN: 38680

South Asian (SAS) AF: 0.00 AC: 0 AN: 82322

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5592

European-Non Finnish (NFE) AF: 0.000104 AC: 114 AN: 1095844

Other (OTH) AF: 0.000323 AC: 19 AN: 58748

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 152058 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74286

African (AFR) AF: 0.00 AC: 0 AN: 41400

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000847 Hom.: 0

Bravo AF: 0.0000340

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000117 AC: 1

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.000221

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.511G>A (p.V171I) alteration is located in exon 6 (coding exon 6) of the SCFD1 gene. This alteration results from a G to A substitution at nucleotide position 511, causing the valine (V) at amino acid position 171 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.35
DEOGEN2	Benign	0.12	T;.;T;.;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.83
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.87	D;D;D;D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.053	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N;.;.;.;.;.
PhyloP100		1.7
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.32	N;N;N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.88	T;T;T;T;T;T
Sift4G	Benign	0.97	T;T;T;T;T;T
Polyphen		0.0	B;.;.;.;.;.
Vest4		0.23
MVP		0.39
MPC		0.29
ClinPred		0.022	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.017
gMVP		0.13
Mutation Taster		=89/11	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: rs376363317; hg19: chr14-31109058;