19-19025490-T-C

Position:

• chr19-19025490-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001017392.5(SUGP2):​c.858A>G​(p.Pro286Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00257 in 1,614,186 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.013 (40 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (31 hom.)
• Consequence: SUGP2 NM_001017392.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830

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]

SUGP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0135 (2053/152298) while in subpopulation AFR AF= 0.0445 (1848/41558). AF 95% confidence interval is 0.0428. There are 40 homozygotes in gnomad4. There are 997 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 40 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUGP2	NM_001017392.5	c.858A>G	p.Pro286Pro	synonymous_variant	3/11	ENST00000452918.7	NP_001017392.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUGP2	ENST00000452918.7	c.858A>G	p.Pro286Pro	synonymous_variant	3/11	1	NM_001017392.5	ENSP00000389380.1

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 2036 AN: 152180 Hom.: 40 Cov.: 32

Gnomad AFR AF: 0.0442

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0125

GnomAD3 exomes AF: 0.00366 AC: 921 AN: 251438 Hom.: 18 AF XY: 0.00300 AC XY: 408 AN XY: 135906

Gnomad AFR exome AF: 0.0464

Gnomad AMR exome AF: 0.00315

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00144 AC: 2103 AN: 1461888 Hom.: 31 Cov.: 32 AF XY: 0.00125 AC XY: 906 AN XY: 727242

Gnomad4 AFR exome AF: 0.0444

Gnomad4 AMR exome AF: 0.00411

Gnomad4 ASJ exome AF: 0.00107

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000119

Gnomad4 OTH exome AF: 0.00384

GnomAD4 genome AF: 0.0135 AC: 2053 AN: 152298 Hom.: 40 Cov.: 32 AF XY: 0.0134 AC XY: 997 AN XY: 74480

Gnomad4 AFR AF: 0.0445

Gnomad4 AMR AF: 0.0103

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.00203 Hom.: 2

Bravo AF: 0.0154

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.4
DANN	Benign	0.63

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: rs34471092; hg19: chr19-19136299;