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GeneBe

12-45924968-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004719.3(SCAF11):c.3666A>T(p.Gln1222His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)

Consequence

SCAF11
NM_004719.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.15
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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06668341).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCAF11NM_004719.3 linkuse as main transcriptc.3666A>T p.Gln1222His missense_variant 12/15 ENST00000369367.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCAF11ENST00000369367.8 linkuse as main transcriptc.3666A>T p.Gln1222His missense_variant 12/151 NM_004719.3 P1Q99590-1
SCAF11ENST00000549162.5 linkuse as main transcriptc.3090A>T p.Gln1030His missense_variant 6/91
SCAF11ENST00000465950.5 linkuse as main transcriptc.2721A>T p.Gln907His missense_variant 2/51 Q99590-2
SCAF11ENST00000547950.1 linkuse as main transcriptn.676A>T non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152230
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:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
34
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152230
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74370
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:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

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 GeneticsOct 27, 2021The c.3666A>T (p.Q1222H) alteration is located in exon 12 (coding exon 11) of the SCAF11 gene. This alteration results from a A to T substitution at nucleotide position 3666, causing the glutamine (Q) at amino acid position 1222 to be replaced by a histidine (H). 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
0.21
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
8.2
DANN
Benign
0.97
DEOGEN2
Benign
0.038
T;.;T
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.71
FATHMM_MKL
Benign
0.22
N
LIST_S2
Benign
0.75
T;T;T
M_CAP
Benign
0.0064
T
MetaRNN
Benign
0.067
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.95
L;.;.
MutationTaster
Benign
0.98
N;N;N;N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-1.8
N;N;N
REVEL
Benign
0.051
Sift
Benign
0.034
D;D;D
Sift4G
Benign
0.14
T;T;T
Polyphen
0.087
B;.;.
Vest4
0.20
MutPred
0.26
Loss of solvent accessibility (P = 0.1551);.;.;
MVP
0.19
MPC
0.041
ClinPred
0.20
T
GERP RS
-1.7
Varity_R
0.056
gMVP
0.39

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: rs769188829; hg19: chr12-46318751; API