chr1-35192302-G-A
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_005066.3(SFPQ):c.748C>T(p.Pro250Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000285 in 1,451,040 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00030 ( 3 hom. )
Consequence
SFPQ
NM_005066.3 missense
NM_005066.3 missense
Scores
2
1
15
Clinical Significance
Conservation
PhyloP100: 3.26
Genes affected
SFPQ (HGNC:10774): (splicing factor proline and glutamine rich) Enables DNA binding activity; histone deacetylase binding activity; and protein homodimerization activity. Involved in several processes, including alternative mRNA splicing, via spliceosome; positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; and regulation of transcription by RNA polymerase II. Acts upstream of or within double-strand break repair via homologous recombination. Located in chromatin; nuclear matrix; and paraspeckles. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0074084103).
BS2
High AC in GnomAd4 at 27 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SFPQ | NM_005066.3 | c.748C>T | p.Pro250Ser | missense_variant | 1/10 | ENST00000357214.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SFPQ | ENST00000357214.6 | c.748C>T | p.Pro250Ser | missense_variant | 1/10 | 1 | NM_005066.3 | P1 | |
SFPQ | ENST00000696553.1 | c.811C>T | p.Pro271Ser | missense_variant | 1/10 |
Frequencies
GnomAD3 genomes AF: 0.000178 AC: 27AN: 151694Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000647 AC: 4AN: 61816Hom.: 0 AF XY: 0.0000540 AC XY: 2AN XY: 37068
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GnomAD4 exome AF: 0.000297 AC: 386AN: 1299238Hom.: 3 Cov.: 33 AF XY: 0.000267 AC XY: 171AN XY: 641252
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GnomAD4 genome AF: 0.000178 AC: 27AN: 151802Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74232
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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 19, 2023 | The c.748C>T (p.P250S) alteration is located in exon 1 (coding exon 1) of the SFPQ gene. This alteration results from a C to T substitution at nucleotide position 748, causing the proline (P) at amino acid position 250 to be replaced by a serine (S). 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
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of glycosylation at P250 (P = 0.0244);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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