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GeneBe

4-53145542-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_152540.4(SCFD2):c.1352T>A(p.Leu451Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SCFD2
NM_152540.4 missense

Scores

5
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.21
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.766

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCFD2NM_152540.4 linkuse as main transcriptc.1352T>A p.Leu451Gln missense_variant 5/9 ENST00000401642.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCFD2ENST00000401642.8 linkuse as main transcriptc.1352T>A p.Leu451Gln missense_variant 5/91 NM_152540.4 P1Q8WU76-1
SCFD2ENST00000388940.8 linkuse as main transcriptc.1352T>A p.Leu451Gln missense_variant 5/82 Q8WU76-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251428
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135890
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461824
Hom.:
0
Cov.:
32
AF XY:
0.00000413
AC XY:
3
AN XY:
727208
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 17, 2022The c.1352T>A (p.L451Q) alteration is located in exon 5 (coding exon 5) of the SCFD2 gene. This alteration results from a T to A substitution at nucleotide position 1352, causing the leucine (L) at amino acid position 451 to be replaced by a glutamine (Q). 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
Pathogenic
0.77
BayesDel_addAF
Benign
-0.067
T
BayesDel_noAF
Benign
-0.11
Cadd
Pathogenic
26
Dann
Uncertain
0.99
DEOGEN2
Uncertain
0.66
D;.
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.77
D;D
MetaSVM
Uncertain
0.20
D
MutationAssessor
Benign
2.0
M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.55
T
PROVEAN
Uncertain
-3.1
D;D
REVEL
Pathogenic
0.75
Sift
Uncertain
0.0020
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.93
P;P
Vest4
0.67
MutPred
0.68
Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);
MVP
0.95
MPC
0.69
ClinPred
0.88
D
GERP RS
5.0
Varity_R
0.61
gMVP
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs761040570; hg19: chr4-54011709; API