NM_001017392.5:c.2354T>C

Variant names:

• chr19-19008413-A-G
• rs549354023
• NM_001017392.5:c.2354T>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.2354T>C​(p.Met785Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M785V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: SUGP2 NM_001017392.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.36
• 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=0.13645929).

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.2354T>C	p.Met785Thr	missense	Exon 6 of 11	NP_001017392.2	Q8IX01-1
	SUGP2	NM_001321698.1		c.2396T>C	p.Met799Thr	missense	Exon 6 of 11	NP_001308627.1	M0R2Z9
	SUGP2	NM_001321699.1		c.2396T>C	p.Met799Thr	missense	Exon 6 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.2354T>C	p.Met785Thr	missense	Exon 6 of 11	ENSP00000389380.1	Q8IX01-1
	SUGP2	ENST00000337018.10	TSL:1	c.2354T>C	p.Met785Thr	missense	Exon 6 of 11	ENSP00000337926.5	Q8IX01-1
	SUGP2	ENST00000330854.15	TSL:1	n.2354T>C		non_coding_transcript_exon	Exon 6 of 13	ENSP00000332373.10	Q8IX01-4

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152106 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251488 AF XY: 0.0000221

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461758 Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6 AN XY: 727188

African (AFR) AF: 0.0000896 AC: 3 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111898

Other (OTH) AF: 0.0000828 AC: 5 AN: 60390

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152224 Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3 AN XY: 74424

African (AFR) AF: 0.0000963 AC: 4 AN: 41530

American (AMR) AF: 0.000131 AC: 2 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000604

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.082
Sift	Uncertain	0.012	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.51
MVP		0.068
MPC		0.37
ClinPred		0.39	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.73
Mutation Taster		=91/9	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: rs549354023; hg19: chr19-19119222;