19-19004333-C-G

Variant names:

• chr19-19004333-C-G
• rs763972693
• NM_001017392.5:c.2764G>C

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.2764G>C​(p.Asp922His) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. D922N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SUGP2 NM_001017392.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.676
• 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=0.22460067).

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.2764G>C	p.Asp922His	missense	Exon 7 of 11	NP_001017392.2	Q8IX01-1
	SUGP2	NM_001321698.1		c.2806G>C	p.Asp936His	missense	Exon 7 of 11	NP_001308627.1	M0R2Z9
	SUGP2	NM_001321699.1		c.2806G>C	p.Asp936His	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.2764G>C	p.Asp922His	missense	Exon 7 of 11	ENSP00000389380.1	Q8IX01-1
	SUGP2	ENST00000337018.10	TSL:1	c.2764G>C	p.Asp922His	missense	Exon 7 of 11	ENSP00000337926.5	Q8IX01-1
	SUGP2	ENST00000330854.15	TSL:1	n.2668-60G>C		intron	N/A	ENSP00000332373.10	Q8IX01-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0049	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.68
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.12
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.24
MutPred		0.14		Gain of catalytic residue at D922 (P = 0.1327)
MVP		0.068
MPC		0.79
ClinPred		0.68	D
GERP RS		5.1
Varity_R		0.10
gMVP		0.69
Mutation Taster		=95/5	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

Other links and lift over

dbSNP: rs763972693; hg19: chr19-19115142;