chr19-19001632-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001017392.5(SUGP2):​c.2972G>T​(p.Arg991Leu) 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 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R991C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SUGP2
NM_001017392.5 missense

Scores

7
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.53
Variant links:
Genes affected
SUGP2 (HGNC:18641): (SURP and G-patch domain containing 2) This gene encodes a member of the arginine/serine-rich family of splicing factors. The encoded protein functions in mRNA processing. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2009]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30745053).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SUGP2NM_001017392.5 linkc.2972G>T p.Arg991Leu missense_variant Exon 8 of 11 ENST00000452918.7 NP_001017392.2 Q8IX01-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SUGP2ENST00000452918.7 linkc.2972G>T p.Arg991Leu missense_variant Exon 8 of 11 1 NM_001017392.5 ENSP00000389380.1 Q8IX01-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461860
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.021
T;T;T;.
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.88
.;.;D;D
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.31
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.0
M;M;M;.
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-2.0
N;N;.;.
REVEL
Benign
0.085
Sift
Uncertain
0.025
D;D;.;.
Sift4G
Benign
0.24
T;T;T;T
Polyphen
0.97
D;D;D;.
Vest4
0.55
MutPred
0.34
Loss of MoRF binding (P = 0.0277);Loss of MoRF binding (P = 0.0277);Loss of MoRF binding (P = 0.0277);.;
MVP
0.068
MPC
0.56
ClinPred
0.97
D
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.19
gMVP
0.67

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-19112441; API