20-62709380-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002531.3(NTSR1):c.173C>T(p.Thr58Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0032 in 1,609,036 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (16 hom.)
• Consequence: NTSR1 NM_002531.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.82

Genes affected

NTSR1 (HGNC:8039): (neurotensin receptor 1) Neurotensin receptor 1 belongs to the large superfamily of G-protein coupled receptors. NTSR1 mediates the multiple functions of neurotensin, such as hypotension, hyperglycemia, hypothermia, antinociception, and regulation of intestinal motility and secretion. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009284794).
• BP6: Variant 20-62709380-C-T is Benign according to our data. Variant chr20-62709380-C-T is described in ClinVar as [Benign]. Clinvar id is 708254.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTSR1	NM_002531.3	c.173C>T	p.Thr58Ile	missense_variant	1/4	ENST00000370501.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTSR1	ENST00000370501.4	c.173C>T	p.Thr58Ile	missense_variant	1/4	1	NM_002531.3	P1

Frequencies

GnomAD3 genomes AF: 0.00294 AC: 448 AN: 152274 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000506

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.0147

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00362

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00331 AC: 814 AN: 246218 Hom.: 5 AF XY: 0.00323 AC XY: 432 AN XY: 133688

Gnomad AFR exome AF: 0.000562

Gnomad AMR exome AF: 0.00128

Gnomad ASJ exome AF: 0.00162

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000954

Gnomad FIN exome AF: 0.0127

Gnomad NFE exome AF: 0.00382

Gnomad OTH exome AF: 0.00430

GnomAD4 exome AF: 0.00323 AC: 4703 AN: 1456644 Hom.: 16 Cov.: 32 AF XY: 0.00311 AC XY: 2251 AN XY: 723812

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.00123

Gnomad4 ASJ exome AF: 0.00242

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000732

Gnomad4 FIN exome AF: 0.0110

Gnomad4 NFE exome AF: 0.00340

Gnomad4 OTH exome AF: 0.00283

GnomAD4 genome AF: 0.00294 AC: 448 AN: 152392 Hom.: 0 Cov.: 33 AF XY: 0.00349 AC XY: 260 AN XY: 74518

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.000784

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0147

Gnomad4 NFE AF: 0.00362

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00342 Hom.: 3

Bravo AF: 0.00214

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00279 AC: 24

ExAC AF: 0.00320 AC: 388

EpiCase AF: 0.00245

EpiControl AF: 0.00362

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

Apr 07, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.16
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0093	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.27
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.025	D
Polyphen		1.0	D
Vest4		0.76
MVP		0.68
MPC		1.1
ClinPred		0.031	T
GERP RS		3.2
Varity_R		0.32
gMVP		0.54

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: rs34257083; hg19: chr20-61340732;