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GeneBe

12-45925071-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004719.3(SCAF11):c.3563C>G(p.Ser1188Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000555 in 1,442,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.0000055 ( 0 hom. )

Consequence

SCAF11
NM_004719.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.78
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.045810997).
BS2
High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCAF11NM_004719.3 linkuse as main transcriptc.3563C>G p.Ser1188Cys missense_variant 12/15 ENST00000369367.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCAF11ENST00000369367.8 linkuse as main transcriptc.3563C>G p.Ser1188Cys missense_variant 12/151 NM_004719.3 P1Q99590-1
SCAF11ENST00000549162.5 linkuse as main transcriptc.2987C>G p.Ser996Cys missense_variant 6/91
SCAF11ENST00000465950.5 linkuse as main transcriptc.2618C>G p.Ser873Cys missense_variant 2/51 Q99590-2
SCAF11ENST00000547950.1 linkuse as main transcriptn.573C>G non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000209
AC:
5
AN:
239702
Hom.:
0
AF XY:
0.0000153
AC XY:
2
AN XY:
130316
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000280
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000555
AC:
8
AN:
1442680
Hom.:
0
Cov.:
33
AF XY:
0.00000140
AC XY:
1
AN XY:
715496
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000204
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
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1

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 GeneticsMay 30, 2023The c.3563C>G (p.S1188C) alteration is located in exon 12 (coding exon 11) of the SCAF11 gene. This alteration results from a C to G substitution at nucleotide position 3563, causing the serine (S) at amino acid position 1188 to be replaced by a cysteine (C). 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
0.097
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
21
DANN
Benign
0.91
DEOGEN2
Benign
0.027
T;.;T
Eigen
Benign
-0.19
Eigen_PC
Benign
-0.051
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.74
T;T;T
M_CAP
Benign
0.0093
T
MetaRNN
Benign
0.046
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.0
L;.;.
MutationTaster
Benign
0.99
N;N;N;N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-1.9
N;N;N
REVEL
Benign
0.050
Sift
Benign
0.11
T;T;T
Sift4G
Uncertain
0.055
T;T;T
Polyphen
0.016
B;.;.
Vest4
0.13
MutPred
0.21
Loss of phosphorylation at S1188 (P = 0.0249);.;.;
MVP
0.10
MPC
0.040
ClinPred
0.13
T
GERP RS
3.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.074
gMVP
0.17

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: rs779566035; hg19: chr12-46318854; API