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GeneBe

12-45922974-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004719.3(SCAF11):c.4087G>T(p.Ala1363Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SCAF11
NM_004719.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.97
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.05851701).
BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCAF11NM_004719.3 linkuse as main transcriptc.4087G>T p.Ala1363Ser missense_variant 13/15 ENST00000369367.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCAF11ENST00000369367.8 linkuse as main transcriptc.4087G>T p.Ala1363Ser missense_variant 13/151 NM_004719.3 P1Q99590-1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152188
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251318
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135818
show subpopulations
Gnomad AFR exome
AF:
0.0000615
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:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461876
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152188
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.000145
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189

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 GeneticsApr 05, 2023The c.4087G>T (p.A1363S) alteration is located in exon 13 (coding exon 12) of the SCAF11 gene. This alteration results from a G to T substitution at nucleotide position 4087, causing the alanine (A) at amino acid position 1363 to be replaced by a serine (S). 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
0.11
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
16
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0080
T;.;T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.19
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.52
T;T;T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.059
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;.;.
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.43
T
PROVEAN
Benign
0.70
N;N;N
REVEL
Benign
0.038
Sift
Benign
0.082
T;T;T
Sift4G
Benign
0.62
T;T;T
Polyphen
0.0020
B;.;.
Vest4
0.11
MutPred
0.31
Gain of phosphorylation at A1363 (P = 0.0119);.;.;
MVP
0.12
MPC
0.036
ClinPred
0.16
T
GERP RS
4.9
Varity_R
0.037
gMVP
0.092

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.16
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: rs932048382; hg19: chr12-46316757; API