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GeneBe

12-45924904-G-A

Variant summary

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

The NM_004719.3(SCAF11):c.3730C>T(p.Arg1244Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000026 in 1,613,992 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: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

SCAF11
NM_004719.3 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.08
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=0.21948054).
BS2
High AC in GnomAdExome4 at 39 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCAF11NM_004719.3 linkuse as main transcriptc.3730C>T p.Arg1244Cys missense_variant 12/15 ENST00000369367.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCAF11ENST00000369367.8 linkuse as main transcriptc.3730C>T p.Arg1244Cys missense_variant 12/151 NM_004719.3 P1Q99590-1
SCAF11ENST00000549162.5 linkuse as main transcriptc.3154C>T p.Arg1052Cys missense_variant 6/91
SCAF11ENST00000465950.5 linkuse as main transcriptc.2785C>T p.Arg929Cys missense_variant 2/51 Q99590-2
SCAF11ENST00000547950.1 linkuse as main transcript downstream_gene_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152118
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000439
AC:
11
AN:
250552
Hom.:
0
AF XY:
0.0000664
AC XY:
9
AN XY:
135518
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000359
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000267
AC:
39
AN:
1461874
Hom.:
0
Cov.:
34
AF XY:
0.0000399
AC XY:
29
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000267
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152118
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000540
Hom.:
0
Bravo
AF:
0.0000340
ExAC
AF:
0.0000330
AC:
4

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 GeneticsFeb 14, 2023The c.3730C>T (p.R1244C) alteration is located in exon 12 (coding exon 11) of the SCAF11 gene. This alteration results from a C to T substitution at nucleotide position 3730, causing the arginine (R) at amino acid position 1244 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
0.22
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.23
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Benign
0.20
T;.;T
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;D;D
M_CAP
Benign
0.078
D
MetaRNN
Benign
0.22
T;T;T
MetaSVM
Benign
-0.78
T
MutationAssessor
Benign
2.0
M;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Benign
0.36
T
PROVEAN
Uncertain
-3.9
D;D;D
REVEL
Uncertain
0.30
Sift
Pathogenic
0.0
D;D;D
Sift4G
Uncertain
0.0020
D;D;D
Polyphen
1.0
D;.;.
Vest4
0.49
MutPred
0.41
Gain of catalytic residue at Q1243 (P = 0.0037);.;.;
MVP
0.17
MPC
0.25
ClinPred
0.83
D
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.46
gMVP
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs557535562; hg19: chr12-46318687; COSMIC: COSV65475095; COSMIC: COSV65475095; API