Menu
GeneBe

12-45926414-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004719.3(SCAF11):c.3287G>A(p.Arg1096Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

SCAF11
NM_004719.3 missense

Scores

3
3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.17
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.13361666).
BS2
High AC in GnomAdExome4 at 28 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCAF11NM_004719.3 linkuse as main transcriptc.3287G>A p.Arg1096Gln missense_variant 11/15 ENST00000369367.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCAF11ENST00000369367.8 linkuse as main transcriptc.3287G>A p.Arg1096Gln missense_variant 11/151 NM_004719.3 P1Q99590-1
SCAF11ENST00000549162.5 linkuse as main transcriptc.2711G>A p.Arg904Gln missense_variant 5/91
SCAF11ENST00000465950.5 linkuse as main transcriptc.2342G>A p.Arg781Gln missense_variant 1/51 Q99590-2
SCAF11ENST00000547950.1 linkuse as main transcriptn.297G>A non_coding_transcript_exon_variant 1/22

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152148
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251296
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135862
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000192
AC:
28
AN:
1461886
Hom.:
0
Cov.:
33
AF XY:
0.0000275
AC XY:
20
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000197
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152148
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000611
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 GeneticsJul 27, 2022The c.3287G>A (p.R1096Q) alteration is located in exon 11 (coding exon 10) of the SCAF11 gene. This alteration results from a G to A substitution at nucleotide position 3287, causing the arginine (R) at amino acid position 1096 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
Benign
0.091
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.34
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.044
T;.;T
Eigen
Pathogenic
0.69
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.13
T;T;T
MetaSVM
Benign
-0.78
T
MutationAssessor
Benign
2.0
M;.;.
MutationTaster
Benign
0.97
N;N;N;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.89
N;N;N
REVEL
Benign
0.19
Sift
Uncertain
0.0050
D;D;D
Sift4G
Benign
0.068
T;T;T
Polyphen
1.0
D;.;D
Vest4
0.17
MutPred
0.27
Loss of MoRF binding (P = 0.0099);.;.;
MVP
0.43
MPC
0.11
ClinPred
0.31
T
GERP RS
5.8
Varity_R
0.094
gMVP
0.12

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

LitVar

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

Other links and lift over

dbSNP: rs776615387; hg19: chr12-46320197; API