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GeneBe

12-45922062-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004719.3(SCAF11):c.4378A>G(p.Lys1460Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 6.9e-7 ( 0 hom. )

Consequence

SCAF11
NM_004719.3 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.82
Variant links:
Genes affected
SCAF11 (HGNC:10784): (SR-related CTD associated factor 11) Enables RNA binding activity. Involved in spliceosomal complex assembly. Located in nuclear body and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10786888).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCAF11NM_004719.3 linkuse as main transcriptc.4378A>G p.Lys1460Glu missense_variant 15/15 ENST00000369367.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCAF11ENST00000369367.8 linkuse as main transcriptc.4378A>G p.Lys1460Glu missense_variant 15/151 NM_004719.3 P1Q99590-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459176
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
725880
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 GeneticsOct 16, 2023The c.4378A>G (p.K1460E) alteration is located in exon 15 (coding exon 14) of the SCAF11 gene. This alteration results from a A to G substitution at nucleotide position 4378, causing the lysine (K) at amino acid position 1460 to be replaced by a glutamic acid (E). 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
0.16
BayesDel_addAF
Benign
-0.090
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.028
T;.;T
Eigen
Benign
-0.14
Eigen_PC
Benign
-0.029
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.64
T;T;T
M_CAP
Benign
0.0081
T
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.0
N;.;.
MutationTaster
Benign
0.95
N;N;N;N
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-1.4
N;N;N
REVEL
Benign
0.057
Sift
Uncertain
0.0020
D;D;D
Sift4G
Uncertain
0.013
D;D;D
Polyphen
0.068
B;.;.
Vest4
0.24
MutPred
0.21
Loss of ubiquitination at K1460 (P = 6e-04);.;.;
MVP
0.19
MPC
1.6
ClinPred
0.80
D
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.28
gMVP
0.088

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-46315845; API