Variant chr9-128823793-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate

The NM_016390.4(SPOUT1):c.1016A>G(p.Tyr339Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,456,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SPOUT1
NM_016390.4 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 6.11

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 Likely_pathogenic. Variant got 8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.947

PP5

Variant 9-128823793-T-C is Pathogenic according to our data. Variant chr9-128823793-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3236476.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SPOUT1	NM_016390.4 linkuse as main transcript	c.1016A>G	p.Tyr339Cys	missense_variant	11/12	ENST00000361256.10
KYAT1-SPOUT1	NR_182311.1 linkuse as main transcript	n.2927A>G		non_coding_transcript_exon_variant	24/25
KYAT1-SPOUT1	NM_001414398.1 linkuse as main transcript	c.2363A>G	p.Tyr788Cys	missense_variant	22/23
KYAT1-SPOUT1	NR_182310.1 linkuse as main transcript	n.2959A>G		non_coding_transcript_exon_variant	24/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SPOUT1	ENST00000361256.10 linkuse as main transcript	c.1016A>G	p.Tyr339Cys	missense_variant	11/12	1	NM_016390.4	P1
SPOUT1	ENST00000467582.1 linkuse as main transcript	c.155+279A>G		intron_variant		2
SPOUT1	ENST00000480366.1 linkuse as main transcript	n.579A>G		non_coding_transcript_exon_variant	5/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1456926

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724294

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Neurodevelopmental disorder

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Columbia University Laboratory of Personalized Genomic Medicine, Columbia University Medical Center

May 20, 2024

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.017

MetaRNN

Pathogenic

0.95

MetaSVM

Benign

-0.65

MutationTaster

Benign

1.0

PROVEAN

Pathogenic

-8.0

REVEL

Uncertain

0.62

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.96

MutPred

0.75

Loss of phosphorylation at Y339 (P = 0.0418);

MVP

0.68

MPC

1.1

ClinPred

0.99

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.90

gMVP

0.87

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