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GeneBe

12-45924914-C-G

Variant summary

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

The NM_004719.3(SCAF11):c.3720G>C(p.Met1240Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000209 in 1,614,040 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

SCAF11
NM_004719.3 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.05
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=0.17012975).
BS2
High AC in GnomAd4 at 18 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCAF11NM_004719.3 linkuse as main transcriptc.3720G>C p.Met1240Ile missense_variant 12/15 ENST00000369367.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCAF11ENST00000369367.8 linkuse as main transcriptc.3720G>C p.Met1240Ile missense_variant 12/151 NM_004719.3 P1Q99590-1
SCAF11ENST00000549162.5 linkuse as main transcriptc.3144G>C p.Met1048Ile missense_variant 6/91
SCAF11ENST00000465950.5 linkuse as main transcriptc.2775G>C p.Met925Ile missense_variant 2/51 Q99590-2
SCAF11ENST00000547950.1 linkuse as main transcript downstream_gene_variant 2

Frequencies

GnomAD3 genomes
AF:
0.000118
AC:
18
AN:
152052
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000136
AC:
34
AN:
250198
Hom.:
0
AF XY:
0.000133
AC XY:
18
AN XY:
135346
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:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000293
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000219
AC:
320
AN:
1461870
Hom.:
1
Cov.:
34
AF XY:
0.000188
AC XY:
137
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000282
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.000118
AC:
18
AN:
152170
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000341
Hom.:
0
Bravo
AF:
0.000151
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.000140
AC:
17
EpiCase
AF:
0.000273
EpiControl
AF:
0.000415

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 GeneticsJun 11, 2021The c.3720G>C (p.M1240I) alteration is located in exon 12 (coding exon 11) of the SCAF11 gene. This alteration results from a G to C substitution at nucleotide position 3720, causing the methionine (M) at amino acid position 1240 to be replaced by an isoleucine (I). 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
0.60
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.35
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T;.;T
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.91
D;D;D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.17
T;T;T
MetaSVM
Benign
-0.72
T
MutationAssessor
Uncertain
2.0
M;.;.
MutationTaster
Benign
0.69
D;D;D;D
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-1.6
N;N;N
REVEL
Benign
0.15
Sift
Benign
0.037
D;D;D
Sift4G
Benign
0.12
T;T;T
Polyphen
0.85
P;.;.
Vest4
0.51
MutPred
0.37
Gain of catalytic residue at V1235 (P = 0);.;.;
MVP
0.22
MPC
0.050
ClinPred
0.17
T
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.30
gMVP
0.15

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: rs146401933; hg19: chr12-46318697; API