19-19025490-T-C

Variant names:

• chr19-19025490-T-C
• rs34471092
• NM_001017392.5:c.858A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 40 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUGP2	NM_001017392.5	MANE Select	c.858A>G	p.Pro286Pro	synonymous	Exon 3 of 11	NP_001017392.2
	SUGP2	NM_001321698.1		c.900A>G	p.Pro300Pro	synonymous	Exon 3 of 11	NP_001308627.1
	SUGP2	NM_001321699.1		c.900A>G	p.Pro300Pro	synonymous	Exon 3 of 11	NP_001308628.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUGP2	ENST00000452918.7	TSL:1 MANE Select	c.858A>G	p.Pro286Pro	synonymous	Exon 3 of 11	ENSP00000389380.1
	SUGP2	ENST00000337018.10	TSL:1	c.858A>G	p.Pro286Pro	synonymous	Exon 3 of 11	ENSP00000337926.5
	SUGP2	ENST00000330854.15	TSL:1	n.858A>G		non_coding_transcript_exon	Exon 3 of 13	ENSP00000332373.10

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

GnomAD2 exomes AF: 0.00366 AC: 921 AN: 251438 AF XY: 0.00300

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 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

African (AFR) AF: 0.0444 AC: 1486 AN: 33480

American (AMR) AF: 0.00411 AC: 184 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00107 AC: 28 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86256

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

Middle Eastern (MID) AF: 0.00503 AC: 29 AN: 5768

European-Non Finnish (NFE) AF: 0.000119 AC: 132 AN: 1112010

Other (OTH) AF: 0.00384 AC: 232 AN: 60396

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

African (AFR) AF: 0.0445 AC: 1848 AN: 41558

American (AMR) AF: 0.0103 AC: 157 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68016

Other (OTH) AF: 0.0123 AC: 26 AN: 2110

Alfa AF: 0.00249 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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.4
DANN	Benign	0.63
PhyloP100		0.083
Mutation Taster		=100/0	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: rs34471092; hg19: chr19-19136299;