1-7852915-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006786.4(UTS2):c.89C>T(p.Ser30Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,609,578 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0081 (16 hom., cov: 31)
  • Exomes 𝑓: 0.00089 (24 hom.)
• Consequence: UTS2 NM_006786.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.95

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037751496).
• BP6: Variant 1-7852915-G-A is Benign according to our data. Variant chr1-7852915-G-A is described in ClinVar as [Benign]. Clinvar id is 709174.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00808 (1230/152148) while in subpopulation AFR AF= 0.0284 (1179/41508). AF 95% confidence interval is 0.0271. There are 16 homozygotes in gnomad4. There are 569 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UTS2	NM_006786.4	c.89C>T	p.Ser30Phe	missense_variant	1/4	ENST00000361696.10
UTS2	NM_021995.2	c.134C>T	p.Ser45Phe	missense_variant	2/5
UTS2	XM_011540537.3	c.134C>T	p.Ser45Phe	missense_variant	3/6
UTS2	XM_011540538.2	c.89C>T	p.Ser30Phe	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UTS2	ENST00000361696.10	c.89C>T	p.Ser30Phe	missense_variant	1/4	1	NM_006786.4	P2
UTS2	ENST00000054668.5	c.134C>T	p.Ser45Phe	missense_variant	2/5	1		A2
UTS2	ENST00000377516.6	c.89C>T	p.Ser30Phe	missense_variant	2/7	5

Frequencies

GnomAD3 genomes AF: 0.00808 AC: 1229 AN: 152032 Hom.: 16 Cov.: 31

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.00211 AC: 519 AN: 246094 Hom.: 6 AF XY: 0.00155 AC XY: 207 AN XY: 133236

Gnomad AFR exome AF: 0.0287

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000715

Gnomad OTH exome AF: 0.00151

GnomAD4 exome AF: 0.000889 AC: 1296 AN: 1457430 Hom.: 24 Cov.: 31 AF XY: 0.000774 AC XY: 561 AN XY: 724866

Gnomad4 AFR exome AF: 0.0321

Gnomad4 AMR exome AF: 0.00164

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000588

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000369

Gnomad4 OTH exome AF: 0.00184

GnomAD4 genome AF: 0.00808 AC: 1230 AN: 152148 Hom.: 16 Cov.: 31 AF XY: 0.00765 AC XY: 569 AN XY: 74406

Gnomad4 AFR AF: 0.0284

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00522

Alfa AF: 0.00193 Hom.: 14

Bravo AF: 0.00942

ESP6500AA AF: 0.0254 AC: 112

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00260 AC: 316

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 13, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	19
Dann	Uncertain	0.99
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.57	T;T;T
MetaRNN	Benign	0.0038	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.97	D;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-4.7	D;D;D
REVEL	Benign	0.027
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.011	D;D;D
Polyphen		0.051	B;B;B
Vest4		0.16
MVP		0.54
MPC		0.65
ClinPred		0.063	T
GERP RS		1.1
Varity_R		0.12
gMVP		0.082

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs116479836; hg19: chr1-7912975;