rs1051219

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004592.4(SFSWAP):​c.1164C>A​(p.Asp388Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SFSWAP
NM_004592.4 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.06

Publications

0 publications found
Variant links:
Genes affected
SFSWAP (HGNC:10790): (splicing factor SWAP) This gene encodes a human homolog of Drosophila splicing regulatory protein. This gene autoregulates its expression by control of splicing of its first two introns. In addition, it also regulates the splicing of fibronectin and CD45 genes. Two transcript variants encoding different isoforms have been identified. [provided by RefSeq, May 2012]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.35351345).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SFSWAPNM_004592.4 linkc.1164C>A p.Asp388Glu missense_variant Exon 8 of 18 ENST00000261674.9 NP_004583.2 Q12872-1Q8IV81

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SFSWAPENST00000261674.9 linkc.1164C>A p.Asp388Glu missense_variant Exon 8 of 18 1 NM_004592.4 ENSP00000261674.4 Q12872-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461886
Hom.:
0
Cov.:
38
AF XY:
0.00
AC XY:
0
AN XY:
727244
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1112008
Other (OTH)
AF:
0.00
AC:
0
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
0.026
DANN
Uncertain
0.98
DEOGEN2
Benign
0.062
T;.
Eigen
Benign
-0.89
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.35
N
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.35
T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
1.2
L;L
PhyloP100
-1.1
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-0.93
N;N
REVEL
Benign
0.12
Sift
Benign
0.25
T;T
Sift4G
Benign
0.36
T;T
Polyphen
0.21
B;.
Vest4
0.16
MutPred
0.37
Gain of catalytic residue at Y392 (P = 0);Gain of catalytic residue at Y392 (P = 0);
MVP
0.082
MPC
0.74
ClinPred
0.58
D
GERP RS
-4.4
PromoterAI
-0.12
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.055
gMVP
0.32
Mutation Taster
=87/13
polymorphism

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

Other links and lift over

dbSNP: rs1051219; hg19: chr12-132237750; API