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GeneBe

12-45926526-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004719.3(SCAF11):c.3175T>C(p.Trp1059Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SCAF11
NM_004719.3 missense

Scores

6
5
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.11
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3158818).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCAF11NM_004719.3 linkuse as main transcriptc.3175T>C p.Trp1059Arg missense_variant 11/15 ENST00000369367.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCAF11ENST00000369367.8 linkuse as main transcriptc.3175T>C p.Trp1059Arg missense_variant 11/151 NM_004719.3 P1Q99590-1
SCAF11ENST00000549162.5 linkuse as main transcriptc.2599T>C p.Trp867Arg missense_variant 5/91
SCAF11ENST00000465950.5 linkuse as main transcriptc.2230T>C p.Trp744Arg missense_variant 1/51 Q99590-2
SCAF11ENST00000547950.1 linkuse as main transcriptn.185T>C non_coding_transcript_exon_variant 1/22

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460768
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
726642
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
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 GeneticsNov 10, 2022The c.3175T>C (p.W1059R) alteration is located in exon 11 (coding exon 10) of the SCAF11 gene. This alteration results from a T to C substitution at nucleotide position 3175, causing the tryptophan (W) at amino acid position 1059 to be replaced by an arginine (R). 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
0.82
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.39
T;.;T
Eigen
Uncertain
0.66
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.82
T;T;T
M_CAP
Benign
0.049
D
MetaRNN
Benign
0.32
T;T;T
MetaSVM
Benign
-0.41
T
MutationAssessor
Uncertain
2.1
M;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.73
T
PROVEAN
Uncertain
-3.0
D;D;D
REVEL
Benign
0.26
Sift
Pathogenic
0.0
D;D;D
Sift4G
Benign
0.38
T;T;T
Polyphen
1.0
D;.;D
Vest4
0.27
MutPred
0.30
Gain of catalytic residue at F1063 (P = 0.0178);.;.;
MVP
0.52
MPC
0.35
ClinPred
1.0
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.59
gMVP
0.13

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: chr12-46320309; API