rs228648

Variant names:

• chr1-7853370-G-A
• rs228648
• ENST00000054668.5:c.62C>T

Variant summary

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

The ENST00000054668.5(UTS2):​c.62C>T​(p.Thr21Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 1,613,688 control chromosomes in the GnomAD database, including 245,554 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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 0.52 (20985 hom., cov: 32)
  • Exomes 𝑓: 0.55 (224569 hom.)
• Consequence: UTS2 ENST00000054668.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.447
• Publications: 71 publications found

Genes affected

UTS2 (HGNC:12636): (urotensin 2) This gene encodes a mature peptide that is an active cyclic heptapeptide absolutely conserved from lamprey to human. The active peptide acts as a vasoconstrictor and is expressed only in brain tissue. Despite the gene family name similarity, this gene is not homologous to urocortin, a member of the sauvagine/corticotropin-releasing factor/urotensin I family. Most of the proprotein is cleaved to make the mature peptide. Transcript variants encoding different preproprotein isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.3832785E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTS2	XM_011540538.2	c.-181C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 5		XP_011538840.1
UTS2	NM_021995.2	c.62C>T	p.Thr21Met	missense_variant	Exon 1 of 5		NP_068835.1
UTS2	XM_011540537.3	c.62C>T	p.Thr21Met	missense_variant	Exon 2 of 6		XP_011538839.1
UTS2	XM_011540538.2	c.-181C>T		5_prime_UTR_variant	Exon 1 of 5		XP_011538840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UTS2	ENST00000054668.5	c.62C>T	p.Thr21Met	missense_variant	Exon 1 of 5	1		ENSP00000054668.5
UTS2	ENST00000377516.6	c.-179C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	5		ENSP00000366738.2
UTS2	ENST00000377516.6	c.-179C>T		5_prime_UTR_variant	Exon 1 of 7	5		ENSP00000366738.2

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78860 AN: 151906 Hom.: 20972 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.551

GnomAD2 exomes AF: 0.513 AC: 128890 AN: 251314 AF XY: 0.529

Gnomad AFR exome AF: 0.468

Gnomad AMR exome AF: 0.318

Gnomad ASJ exome AF: 0.626

Gnomad EAS exome AF: 0.349

Gnomad FIN exome AF: 0.451

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.552

GnomAD4 exome AF: 0.550 AC: 804044 AN: 1461664 Hom.: 224569 Cov.: 50 AF XY: 0.555 AC XY: 403465 AN XY: 727144

African (AFR) AF: 0.465 AC: 15556 AN: 33468

American (AMR) AF: 0.329 AC: 14724 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 16285 AN: 26128

East Asian (EAS) AF: 0.352 AC: 13980 AN: 39678

South Asian (SAS) AF: 0.624 AC: 53843 AN: 86226

European-Finnish (FIN) AF: 0.447 AC: 23863 AN: 53414

Middle Eastern (MID) AF: 0.699 AC: 4033 AN: 5768

European-Non Finnish (NFE) AF: 0.565 AC: 628025 AN: 1111898

Other (OTH) AF: 0.559 AC: 33735 AN: 60386

GnomAD4 genome AF: 0.519 AC: 78902 AN: 152024 Hom.: 20985 Cov.: 32 AF XY: 0.514 AC XY: 38207 AN XY: 74304

African (AFR) AF: 0.473 AC: 19601 AN: 41422

American (AMR) AF: 0.444 AC: 6784 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2143 AN: 3472

East Asian (EAS) AF: 0.354 AC: 1833 AN: 5174

South Asian (SAS) AF: 0.612 AC: 2954 AN: 4824

European-Finnish (FIN) AF: 0.459 AC: 4847 AN: 10556

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38739 AN: 67986

Other (OTH) AF: 0.554 AC: 1169 AN: 2110

Alfa AF: 0.554 Hom.: 112575

Bravo AF: 0.508

TwinsUK AF: 0.567 AC: 2102

ALSPAC AF: 0.551 AC: 2124

ESP6500AA AF: 0.474 AC: 2089

ESP6500EA AF: 0.569 AC: 4895

ExAC AF: 0.523 AC: 63477

Asia WGS AF: 0.502 AC: 1747 AN: 3478

EpiCase AF: 0.579

EpiControl AF: 0.580

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.7
DANN	Benign	0.93
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.0000034	T
MetaSVM	Benign	-0.94	T
PhyloP100		-0.45
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.025
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.033	D
Polyphen		0.22	B
Vest4		0.029
MPC		0.34
ClinPred		0.0029	T
GERP RS		-3.1
PromoterAI		-0.061	Neutral
gMVP		0.067
Mutation Taster		=99/1	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: rs228648; hg19: chr1-7913430; COSMIC: COSV50013105; COSMIC: COSV50013105;