19-19004601-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 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. 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017392.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUGP2	NM_001017392.5	MANE Select	c.2496G>T	p.Lys832Asn	missense	Exon 7 of 11	NP_001017392.2	Q8IX01-1
	SUGP2	NM_001321698.1		c.2538G>T	p.Lys846Asn	missense	Exon 7 of 11	NP_001308627.1	M0R2Z9
	SUGP2	NM_001321699.1		c.2538G>T	p.Lys846Asn	missense	Exon 7 of 11	NP_001308628.1	M0R2Z9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUGP2	ENST00000452918.7	TSL:1 MANE Select	c.2496G>T	p.Lys832Asn	missense	Exon 7 of 11	ENSP00000389380.1	Q8IX01-1
	SUGP2	ENST00000337018.10	TSL:1	c.2496G>T	p.Lys832Asn	missense	Exon 7 of 11	ENSP00000337926.5	Q8IX01-1
	SUGP2	ENST00000330854.15	TSL:1	n.2496G>T		non_coding_transcript_exon	Exon 7 of 13	ENSP00000332373.10	Q8IX01-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.016
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.65	N
PhyloP100		1.7
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.068
Sift	Benign	0.059	T
Sift4G	Benign	0.18	T
Polyphen		0.41	B
Vest4		0.20
MutPred		0.54		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
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs1363449030; hg19: chr19-19115410;