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GeneBe

12-45924804-G-T

Variant summary

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

The NM_004719.3(SCAF11):c.3830C>A(p.Pro1277Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)

Consequence

SCAF11
NM_004719.3 missense

Scores

5
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.22
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]

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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=0.37786615).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCAF11NM_004719.3 linkuse as main transcriptc.3830C>A p.Pro1277Gln missense_variant 12/15 ENST00000369367.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCAF11ENST00000369367.8 linkuse as main transcriptc.3830C>A p.Pro1277Gln missense_variant 12/151 NM_004719.3 P1Q99590-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
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 GeneticsAug 11, 2022The c.3830C>A (p.P1277Q) alteration is located in exon 12 (coding exon 11) of the SCAF11 gene. This alteration results from a C to A substitution at nucleotide position 3830, causing the proline (P) at amino acid position 1277 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
0.64
BayesDel_addAF
Uncertain
0.036
T
BayesDel_noAF
Benign
-0.19
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.44
T;.;T
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.88
D;D;D
M_CAP
Benign
0.042
D
MetaRNN
Benign
0.38
T;T;T
MetaSVM
Benign
-0.41
T
MutationAssessor
Benign
2.0
M;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.58
T
PROVEAN
Pathogenic
-5.0
D;D;D
REVEL
Benign
0.27
Sift
Uncertain
0.0010
D;D;D
Sift4G
Uncertain
0.0030
D;D;D
Polyphen
1.0
D;.;.
Vest4
0.48
MutPred
0.26
Gain of catalytic residue at L1276 (P = 0);.;.;
MVP
0.26
MPC
0.27
ClinPred
0.99
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.53
gMVP
0.61

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: chr12-46318587; API