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GeneBe

12-45925014-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_004719.3(SCAF11):c.3620T>C(p.Met1207Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,870 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M1207I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SCAF11
NM_004719.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.38
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 -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10048172).
BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCAF11NM_004719.3 linkuse as main transcriptc.3620T>C p.Met1207Thr missense_variant 12/15 ENST00000369367.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCAF11ENST00000369367.8 linkuse as main transcriptc.3620T>C p.Met1207Thr missense_variant 12/151 NM_004719.3 P1Q99590-1
SCAF11ENST00000549162.5 linkuse as main transcriptc.3044T>C p.Met1015Thr missense_variant 6/91
SCAF11ENST00000465950.5 linkuse as main transcriptc.2675T>C p.Met892Thr missense_variant 2/51 Q99590-2
SCAF11ENST00000547950.1 linkuse as main transcriptn.630T>C non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
249042
Hom.:
0
AF XY:
0.0000223
AC XY:
3
AN XY:
134806
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
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:
0.00000342
AC:
5
AN:
1461870
Hom.:
0
Cov.:
34
AF XY:
0.00000550
AC XY:
4
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000894
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
Cov.:
32
Bravo
AF:
0.00000378

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 28, 2023The c.3620T>C (p.M1207T) alteration is located in exon 12 (coding exon 11) of the SCAF11 gene. This alteration results from a T to C substitution at nucleotide position 3620, causing the methionine (M) at amino acid position 1207 to be replaced by a threonine (T). 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
-0.29
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
22
DANN
Benign
0.92
DEOGEN2
Benign
0.041
T;.;T
Eigen
Benign
-0.14
Eigen_PC
Benign
-0.016
FATHMM_MKL
Benign
0.74
D
LIST_S2
Benign
0.75
T;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.10
T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.6
L;.;.
MutationTaster
Benign
0.80
D;D;D;D
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-1.8
N;N;N
REVEL
Benign
0.098
Sift
Uncertain
0.0010
D;D;D
Sift4G
Benign
0.089
T;T;T
Polyphen
0.013
B;.;.
Vest4
0.33
MutPred
0.30
Gain of glycosylation at M1207 (P = 0.0158);.;.;
MVP
0.082
MPC
0.044
ClinPred
0.27
T
GERP RS
3.9
Varity_R
0.50
gMVP
0.15

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: rs1167879112; hg19: chr12-46318797; API