rs10404860

Variant names:

• chr19-19024693-A-G
• rs10404860
• NM_001017392.5:c.1655T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321698.1(SUGP2):​c.1697T>C​(p.Met566Thr) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.037 (322 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (306 hom.)
• Consequence: SUGP2 NM_001321698.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.886
• Publications: 9 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 (MetaRNN=0.0020294785).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321698.1. 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.1655T>C	p.Met552Thr	missense	Exon 3 of 11	NP_001017392.2
	SUGP2	NM_001321698.1		c.1697T>C	p.Met566Thr	missense	Exon 3 of 11	NP_001308627.1
	SUGP2	NM_001321699.1		c.1697T>C	p.Met566Thr	missense	Exon 3 of 11	NP_001308628.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUGP2	ENST00000452918.7	TSL:1 MANE Select	c.1655T>C	p.Met552Thr	missense	Exon 3 of 11	ENSP00000389380.1
	SUGP2	ENST00000337018.10	TSL:1	c.1655T>C	p.Met552Thr	missense	Exon 3 of 11	ENSP00000337926.5
	SUGP2	ENST00000330854.15	TSL:1	n.1655T>C		non_coding_transcript_exon	Exon 3 of 13	ENSP00000332373.10

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

GnomAD2 exomes AF: 0.0101 AC: 2533 AN: 251408 AF XY: 0.00753

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 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

African (AFR) AF: 0.132 AC: 4410 AN: 33478

American (AMR) AF: 0.00935 AC: 418 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00386 AC: 101 AN: 26136

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

South Asian (SAS) AF: 0.000348 AC: 30 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.0111 AC: 64 AN: 5768

European-Non Finnish (NFE) AF: 0.000250 AC: 278 AN: 1112012

Other (OTH) AF: 0.00919 AC: 555 AN: 60396

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

African (AFR) AF: 0.127 AC: 5290 AN: 41534

American (AMR) AF: 0.0187 AC: 286 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3472

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

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 68026

Other (OTH) AF: 0.0298 AC: 63 AN: 2114

Alfa AF: 0.0139 Hom.: 318

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 v4.9

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
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.024	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.89
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.73	N
REVEL	Benign	0.023
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	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
Mutation Taster		=100/0	polymorphism (auto)

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