rs10404860

chr19-19024693-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001017392.5(SUGP2):c.1655T>C(p.Met552Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00715 in 1,614,170 control chromosomes in the GnomAD database, including 628 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.037 (322 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (306 hom.)
• Consequence: SUGP2 NM_001017392.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.886

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020294785).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUGP2	NM_001017392.5	c.1655T>C	p.Met552Thr	missense_variant	3/11	ENST00000452918.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUGP2	ENST00000452918.7	c.1655T>C	p.Met552Thr	missense_variant	3/11	1	NM_001017392.5	P2

Frequencies

GnomAD3 genomes AF: 0.0373 AC: 5676 AN: 152162 Hom.: 322 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0189

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0301

GnomAD3 exomes AF: 0.0101 AC: 2533 AN: 251408 Hom.: 155 AF XY: 0.00753 AC XY: 1024 AN XY: 135900

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.00737

Gnomad ASJ exome AF: 0.00417

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000359

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000475

Gnomad OTH exome AF: 0.00587

GnomAD4 exome AF: 0.00401 AC: 5856 AN: 1461890 Hom.: 306 Cov.: 32 AF XY: 0.00347 AC XY: 2526 AN XY: 727246

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.00935

Gnomad4 ASJ exome AF: 0.00386

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000250

Gnomad4 OTH exome AF: 0.00919

GnomAD4 genome AF: 0.0374 AC: 5692 AN: 152280 Hom.: 322 Cov.: 32 AF XY: 0.0354 AC XY: 2639 AN XY: 74480

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.0187

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.00725 Hom.: 116

Bravo AF: 0.0425

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.129 AC: 567

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.0124 AC: 1509

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.15
Dann	Benign	0.20
DEOGEN2	Benign	0.0019	T;T;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0016	N
MetaRNN	Benign	0.0020	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.34	N;N;N;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.73	N;N;.;.
REVEL	Benign	0.023
Sift	Benign	1.0	T;T;.;.
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	B;B;B;.
Vest4		0.014
MPC		0.22
ClinPred		0.00014	T
GERP RS		-0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.018
gMVP		0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs10404860; hg19: chr19-19135502; COSMIC: COSV58262318; COSMIC: COSV58262318;