chr9-128824961-G-C

Variant names:

• chr9-128824961-G-C
• rs2293968
• NM_016390.4:c.712+16C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016390.4(SPOUT1):​c.712+16C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,450,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SPOUT1 NM_016390.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.406
• Publications: 24 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

KYAT1 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPOUT1	NM_016390.4	c.712+16C>G		intron_variant	Intron 8 of 11	ENST00000361256.10	NP_057474.2
KYAT1-SPOUT1	NM_001414398.1	c.2059+16C>G		intron_variant	Intron 19 of 22		NP_001401327.1
KYAT1-SPOUT1	NR_182310.1	n.2655+16C>G		intron_variant	Intron 21 of 24
KYAT1-SPOUT1	NR_182311.1	n.2623+16C>G		intron_variant	Intron 21 of 24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPOUT1	ENST00000361256.10	c.712+16C>G		intron_variant	Intron 8 of 11	1	NM_016390.4	ENSP00000354812.5
KYAT1	ENST00000651925.1	c.*1751+16C>G		intron_variant	Intron 25 of 28			ENSP00000498386.1
SPOUT1	ENST00000480366.1	n.275+16C>G		intron_variant	Intron 2 of 5	2
SPOUT1	ENST00000467582.1	c.-139C>G		upstream_gene_variant		2		ENSP00000473640.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000431 AC: 1 AN: 232154 AF XY: 0.00000797

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1450804 Hom.: 0 Cov.: 34 AF XY: 0.00000277 AC XY: 2 AN XY: 720822

African (AFR) AF: 0.00 AC: 0 AN: 33372

American (AMR) AF: 0.00 AC: 0 AN: 42562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25912

East Asian (EAS) AF: 0.00 AC: 0 AN: 39404

South Asian (SAS) AF: 0.0000235 AC: 2 AN: 85210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52824

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1105742

Other (OTH) AF: 0.00 AC: 0 AN: 60024

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 19835

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.3
DANN	Benign	0.71
PhyloP100		0.41
PromoterAI		-0.0025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.67		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.67		Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2293968; hg19: chr9-131587240;