NM_016106.4:c.265G>A

Variant names:

• chr14-30633990-G-A
• rs757789677
• NM_016106.4:c.265G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_016106.4(SCFD1):​c.265G>A​(p.Val89Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,452,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: SCFD1 NM_016106.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.04
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17395407).
• BS2: High AC in GnomAdExome4 at 16 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.265G>A	p.Val89Ile	missense	Exon 4 of 25	NP_057190.2
	SCFD1	NM_001283032.1		c.88G>A	p.Val30Ile	missense	Exon 3 of 24	NP_001269961.1	Q8WVM8
	SCFD1	NM_182835.2		c.64G>A	p.Val22Ile	missense	Exon 3 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.265G>A	p.Val89Ile	missense	Exon 4 of 25	ENSP00000390783.2	Q8WVM8-1
	SCFD1	ENST00000555259.5	TSL:1	n.221+3425G>A		intron	N/A	ENSP00000452323.1	G3V5F3
	SCFD1	ENST00000556768.5	TSL:1	n.221+3425G>A		intron	N/A	ENSP00000451811.1	G3V4I1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000808 AC: 2 AN: 247376 AF XY: 0.00

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: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1452786 Hom.: 0 Cov.: 27 AF XY: 0.0000138 AC XY: 10 AN XY: 723098

African (AFR) AF: 0.00 AC: 0 AN: 33022

American (AMR) AF: 0.00 AC: 0 AN: 44256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25972

East Asian (EAS) AF: 0.00 AC: 0 AN: 39212

South Asian (SAS) AF: 0.00 AC: 0 AN: 85266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.0000145 AC: 16 AN: 1106104

Other (OTH) AF: 0.00 AC: 0 AN: 59970

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 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	0.057
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.027
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.085	N
PhyloP100		3.0
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.042
Sift	Benign	0.73	T
Sift4G	Benign	0.69	T
Polyphen		0.0010	B
Vest4		0.24
MutPred		0.58		Loss of phosphorylation at Y90 (P = 0.128)
MVP		0.20
MPC		0.33
ClinPred		0.32	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.027
gMVP		0.12
Mutation Taster		=269/31	polymorphism

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: rs757789677; hg19: chr14-31103196;