19-19025732-C-T

Variant names:

• chr19-19025732-C-T
• rs4808907
• NM_001017392.5:c.616G>A

Variant summary

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

The NM_001017392.5(SUGP2):​c.616G>A​(p.Gly206Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 1,613,592 control chromosomes in the GnomAD database, including 449,067 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.74 (41181 hom., cov: 28)
  • Exomes 𝑓: 0.75 (407886 hom.)
• Consequence: SUGP2 NM_001017392.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800

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=8.473584E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUGP2	NM_001017392.5	c.616G>A	p.Gly206Ser	missense_variant	Exon 3 of 11	ENST00000452918.7	NP_001017392.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUGP2	ENST00000452918.7	c.616G>A	p.Gly206Ser	missense_variant	Exon 3 of 11	1	NM_001017392.5	ENSP00000389380.1

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111487 AN: 151632 Hom.: 41157 Cov.: 28

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.872

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.743

GnomAD3 exomes AF: 0.757 AC: 190255 AN: 251372 Hom.: 72332 AF XY: 0.754 AC XY: 102485 AN XY: 135874

Gnomad AFR exome AF: 0.699

Gnomad AMR exome AF: 0.797

Gnomad ASJ exome AF: 0.750

Gnomad EAS exome AF: 0.880

Gnomad SAS exome AF: 0.749

Gnomad FIN exome AF: 0.719

Gnomad NFE exome AF: 0.743

Gnomad OTH exome AF: 0.756

GnomAD4 exome AF: 0.746 AC: 1090716 AN: 1461842 Hom.: 407886 Cov.: 75 AF XY: 0.746 AC XY: 542233 AN XY: 727222

Gnomad4 AFR exome AF: 0.694

Gnomad4 AMR exome AF: 0.797

Gnomad4 ASJ exome AF: 0.757

Gnomad4 EAS exome AF: 0.897

Gnomad4 SAS exome AF: 0.747

Gnomad4 FIN exome AF: 0.724

Gnomad4 NFE exome AF: 0.741

Gnomad4 OTH exome AF: 0.749

GnomAD4 genome AF: 0.735 AC: 111565 AN: 151750 Hom.: 41181 Cov.: 28 AF XY: 0.735 AC XY: 54493 AN XY: 74126

Gnomad4 AFR AF: 0.697

Gnomad4 AMR AF: 0.774

Gnomad4 ASJ AF: 0.758

Gnomad4 EAS AF: 0.886

Gnomad4 SAS AF: 0.750

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.738

Gnomad4 OTH AF: 0.741

Alfa AF: 0.745 Hom.: 103832

Bravo AF: 0.743

ESP6500AA AF: 0.687 AC: 3028

ESP6500EA AF: 0.743 AC: 6390

ExAC AF: 0.755 AC: 91663

Asia WGS AF: 0.802 AC: 2790 AN: 3478

EpiCase AF: 0.733

EpiControl AF: 0.741

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.27
DEOGEN2	Benign	0.0021	T;T;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0072	N
LIST_S2	Benign	0.21	.;.;T;T
MetaRNN	Benign	8.5e-7	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.81	N;N;N;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.31	N;N;.;.
REVEL	Benign	0.011
Sift	Benign	1.0	T;T;.;.
Sift4G	Benign	0.81	T;T;T;T
Polyphen		0.0	B;B;B;.
Vest4		0.021
MPC		0.19
ClinPred		0.000017	T
GERP RS		-0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.020
gMVP		0.074

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: rs4808907; hg19: chr19-19136541; COSMIC: COSV58258057; COSMIC: COSV58258057;