19-19004601-C-A

Variant names:

• chr19-19004601-C-A
• rs1363449030
• NM_001017392.5:c.2496G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001017392.5(SUGP2):​c.2496G>T​(p.Lys832Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SUGP2 NM_001017392.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21792287).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUGP2	NM_001017392.5	c.2496G>T	p.Lys832Asn	missense_variant	Exon 7 of 11	ENST00000452918.7	NP_001017392.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUGP2	ENST00000452918.7	c.2496G>T	p.Lys832Asn	missense_variant	Exon 7 of 11	1	NM_001017392.5	ENSP00000389380.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0063	T;T;T;.
Eigen	Benign	0.016
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	.;.;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.65	N;N;N;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.36	N;N;.;.
REVEL	Benign	0.068
Sift	Benign	0.059	T;T;.;.
Sift4G	Benign	0.18	T;T;T;T
Polyphen		0.41	B;B;B;.
Vest4		0.20
MutPred		0.54		Loss of methylation at K832 (P = 0.0161);Loss of methylation at K832 (P = 0.0161);Loss of methylation at K832 (P = 0.0161);.;
MVP		0.15
MPC		0.41
ClinPred		0.53	D
GERP RS		5.3
Varity_R		0.076
gMVP		0.59

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

LitVar

Other links and lift over

dbSNP: rs1363449030; hg19: chr19-19115410;