chr6-154832359-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_014892.5(SCAF8):c.2780G>A(p.Arg927His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,726 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
SCAF8
NM_014892.5 missense
NM_014892.5 missense
Scores
5
4
10
Clinical Significance
Conservation
PhyloP100: 9.19
Genes affected
SCAF8 (HGNC:20959): (SR-related CTD associated factor 8) Enables RNA binding activity and RNA polymerase II C-terminal domain phosphoserine binding activity. Involved in negative regulation of termination of RNA polymerase II transcription, poly(A)-coupled and positive regulation of DNA-templated transcription, elongation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM1
In a modified_residue Asymmetric dimethylarginine (size 0) in uniprot entity SCAF8_HUMAN
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCAF8 | NM_014892.5 | c.2780G>A | p.Arg927His | missense_variant | 20/20 | ENST00000367178.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCAF8 | ENST00000367178.8 | c.2780G>A | p.Arg927His | missense_variant | 20/20 | 2 | NM_014892.5 | P1 | |
SCAF8 | ENST00000417268.3 | c.3014G>A | p.Arg1005His | missense_variant | 21/21 | 2 | |||
SCAF8 | ENST00000367186.7 | c.2978G>A | p.Arg993His | missense_variant | 22/22 | 2 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250376Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135360
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461726Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 727178
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GnomAD4 genome Cov.: 31
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31
ExAC
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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 submitter | clinical testing | Ambry Genetics | Jul 20, 2022 | The c.2780G>A (p.R927H) alteration is located in exon 20 (coding exon 20) of the SCAF8 gene. This alteration results from a G to A substitution at nucleotide position 2780, causing the arginine (R) at amino acid position 927 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.
REVEL
Benign
Sift
Pathogenic
D;D;.
Sift4G
Benign
T;T;T
Polyphen
D;.;.
Vest4
MutPred
0.23
.;Loss of loop (P = 0.0512);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at