Variant 9-128822790-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_016390.4(SPOUT1):c.1106T>C(p.Ile369Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 1,587,644 control chromosomes in the GnomAD database, including 424,324 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.64 ( 33989 hom., cov: 34)

Exomes 𝑓: 0.73 ( 390335 hom. )

Consequence

SPOUT1
NM_016390.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.104

Variant links:

Genes affected

SPOUT1 (HGNC:26933): (SPOUT domain containing methyltransferase 1) Enables miRNA binding activity. Involved in maintenance of centrosome location and production of miRNAs involved in gene silencing by miRNA. Located in kinetochore; mitotic spindle; and spindle pole centrosome. [provided by Alliance of Genome Resources, Apr 2022]

SPOUT1 links:

KYAT1-SPOUT1 (HGNC:):

KYAT1-SPOUT1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.326055E-7).

BP6

Variant 9-128822790-A-G is Benign according to our data. Variant chr9-128822790-A-G is described in ClinVar as [Benign]. Clinvar id is 3059891.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SPOUT1	NM_016390.4 linkuse as main transcript	c.1106T>C	p.Ile369Thr	missense_variant	12/12	ENST00000361256.10
KYAT1-SPOUT1	NR_182311.1 linkuse as main transcript	n.3017T>C		non_coding_transcript_exon_variant	25/25
KYAT1-SPOUT1	NM_001414398.1 linkuse as main transcript	c.2453T>C	p.Ile818Thr	missense_variant	23/23
KYAT1-SPOUT1	NR_182310.1 linkuse as main transcript	n.3049T>C		non_coding_transcript_exon_variant	25/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SPOUT1	ENST00000361256.10 linkuse as main transcript	c.1106T>C	p.Ile369Thr	missense_variant	12/12	1	NM_016390.4	P1
SPOUT1	ENST00000467582.1 linkuse as main transcript	c.199T>C	p.Ser67Pro	missense_variant	3/3	2
SPOUT1	ENST00000480366.1 linkuse as main transcript			downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.644

AC:

97950

AN:

152090

Hom.:

33981

Cov.:

show subpopulations

Gnomad AFR

AF:

0.360

Gnomad AMI

AF:

0.794

Gnomad AMR

AF:

0.757

Gnomad ASJ

AF:

0.764

Gnomad EAS

AF:

0.724

Gnomad SAS

AF:

0.615

Gnomad FIN

AF:

0.828

Gnomad MID

AF:

0.633

Gnomad NFE

AF:

0.750

Gnomad OTH

AF:

0.665

GnomAD3 exomes

AF:

0.723

AC:

151701

AN:

209750

Hom.:

56186

AF XY:

0.722

AC XY:

81449

AN XY:

112764

show subpopulations

Gnomad AFR exome

AF:

0.349

Gnomad AMR exome

AF:

0.803

Gnomad ASJ exome

AF:

0.755

Gnomad EAS exome

AF:

0.724

Gnomad SAS exome

AF:

0.625

Gnomad FIN exome

AF:

0.833

Gnomad NFE exome

AF:

0.749

Gnomad OTH exome

AF:

0.732

GnomAD4 exome

AF:

0.734

AC:

1053726

AN:

1435436

Hom.:

390335

Cov.:

AF XY:

0.732

AC XY:

520975

AN XY:

711446

show subpopulations

Gnomad4 AFR exome

AF:

0.347

Gnomad4 AMR exome

AF:

0.799

Gnomad4 ASJ exome

AF:

0.759

Gnomad4 EAS exome

AF:

0.752

Gnomad4 SAS exome

AF:

0.625

Gnomad4 FIN exome

AF:

0.832

Gnomad4 NFE exome

AF:

0.747

Gnomad4 OTH exome

AF:

0.708

GnomAD4 genome

AF:

0.644

AC:

97997

AN:

152208

Hom.:

33989

Cov.:

AF XY:

0.649

AC XY:

48283

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.360

Gnomad4 AMR

AF:

0.757

Gnomad4 ASJ

AF:

0.764

Gnomad4 EAS

AF:

0.724

Gnomad4 SAS

AF:

0.614

Gnomad4 FIN

AF:

0.828

Gnomad4 NFE

AF:

0.750

Gnomad4 OTH

AF:

0.664

Alfa

AF:

0.725

Hom.:

82594

Bravo

AF:

0.629

TwinsUK

AF:

0.752

AC:

2788

ALSPAC

AF:

0.744

AC:

2869

ESP6500AA

AF:

0.377

AC:

1655

ESP6500EA

AF:

0.747

AC:

6411

ExAC

AF:

0.686

AC:

81388

Asia WGS

AF:

0.658

AC:

2287

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SPOUT1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 16, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

3.2

DANN

Benign

0.69

DEOGEN2

Benign

0.015

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.11

MetaRNN

Benign

8.3e-7

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

PROVEAN

Benign

0.84

REVEL

Benign

0.040

Sift

Benign

0.83

Sift4G

Benign

0.65

Polyphen

0.0

Vest4

0.032

MPC

0.51

ClinPred

0.0050

GERP RS

-0.32

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.033

gMVP

0.35

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over