Variant 9-128822807-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_016390.4(SPOUT1):c.1089C>G(p.Ala363=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0178 in 1,591,632 control chromosomes in the GnomAD database, including 313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.014 ( 18 hom., cov: 34)

Exomes 𝑓: 0.018 ( 295 hom. )

Consequence

SPOUT1
NM_016390.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.288

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038615167).

BP6

Variant 9-128822807-G-C is Benign according to our data. Variant chr9-128822807-G-C is described in ClinVar as [Benign]. Clinvar id is 3041881.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.288 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0137 (2086/152364) while in subpopulation NFE AF= 0.0207 (1408/68032). AF 95% confidence interval is 0.0198. There are 18 homozygotes in gnomad4. There are 971 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SPOUT1	NM_016390.4 linkuse as main transcript	c.1089C>G	p.Ala363=	synonymous_variant	12/12	ENST00000361256.10
KYAT1-SPOUT1	NR_182311.1 linkuse as main transcript	n.3000C>G		non_coding_transcript_exon_variant	25/25
KYAT1-SPOUT1	NM_001414398.1 linkuse as main transcript	c.2436C>G	p.Ala812=	synonymous_variant	23/23
KYAT1-SPOUT1	NR_182310.1 linkuse as main transcript	n.3032C>G		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.1089C>G	p.Ala363=	synonymous_variant	12/12	1	NM_016390.4	P1
SPOUT1	ENST00000467582.1 linkuse as main transcript	c.182C>G	p.Pro61Arg	missense_variant	3/3	2
SPOUT1	ENST00000480366.1 linkuse as main transcript	n.652C>G		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes

AF:

0.0137

AC:

2085

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0112

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0230

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0207

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.0135

AC:

2877

AN:

213716

Hom.:

AF XY:

0.0131

AC XY:

1510

AN XY:

115088

show subpopulations

Gnomad AFR exome

AF:

0.00236

Gnomad AMR exome

AF:

0.00913

Gnomad ASJ exome

AF:

0.0176

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00273

Gnomad FIN exome

AF:

0.0217

Gnomad NFE exome

AF:

0.0196

Gnomad OTH exome

AF:

0.0168

GnomAD4 exome

AF:

0.0183

AC:

26324

AN:

1439268

Hom.:

295

Cov.:

AF XY:

0.0179

AC XY:

12753

AN XY:

713844

show subpopulations

Gnomad4 AFR exome

AF:

0.00320

Gnomad4 AMR exome

AF:

0.00990

Gnomad4 ASJ exome

AF:

0.0179

Gnomad4 EAS exome

AF:

0.0000516

Gnomad4 SAS exome

AF:

0.00284

Gnomad4 FIN exome

AF:

0.0228

Gnomad4 NFE exome

AF:

0.0209

Gnomad4 OTH exome

AF:

0.0152

GnomAD4 genome

AF:

0.0137

AC:

2086

AN:

152364

Hom.:

Cov.:

AF XY:

0.0130

AC XY:

971

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00361

Gnomad4 AMR

AF:

0.0113

Gnomad4 ASJ

AF:

0.0193

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.0230

Gnomad4 NFE

AF:

0.0207

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0185

Hom.:

Bravo

AF:

0.0129

TwinsUK

AF:

0.0229

AC:

ALSPAC

AF:

0.0208

AC:

ESP6500AA

AF:

0.00297

AC:

ESP6500EA

AF:

0.0183

AC:

157

ExAC

AF:

0.0116

AC:

1400

Asia WGS

AF:

0.00144

AC:

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

Jun 11, 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

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.4

DANN

Benign

0.83

DEOGEN2

Benign

0.0084

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.29

MetaRNN

Benign

0.0039

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

Sift4G

Uncertain

0.0040

ClinPred

0.0027

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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