rs2293968

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr9-128824961-G-A
• chr9-128824961-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016390.4(SPOUT1):​c.712+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 1,601,352 control chromosomes in the GnomAD database, including 379,418 homozygotes. 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: 𝑓 0.58 (28908 hom., cov: 31)
  • Exomes 𝑓: 0.69 (350510 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPOUT1	NM_016390.4	c.712+16C>T		intron_variant	Intron 8 of 11	ENST00000361256.10	NP_057474.2
KYAT1-SPOUT1	NM_001414398.1	c.2059+16C>T		intron_variant	Intron 19 of 22		NP_001401327.1
KYAT1-SPOUT1	NR_182310.1	n.2655+16C>T		intron_variant	Intron 21 of 24
KYAT1-SPOUT1	NR_182311.1	n.2623+16C>T		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>T		intron_variant	Intron 8 of 11	1	NM_016390.4	ENSP00000354812.5
KYAT1	ENST00000651925.1	c.*1751+16C>T		intron_variant	Intron 25 of 28			ENSP00000498386.1
SPOUT1	ENST00000480366.1	n.275+16C>T		intron_variant	Intron 2 of 5	2
SPOUT1	ENST00000467582.1	c.-139C>T		upstream_gene_variant		2		ENSP00000473640.1

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88227 AN: 151848 Hom.: 28898 Cov.: 31

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.607

GnomAD2 exomes AF: 0.667 AC: 154877 AN: 232154 AF XY: 0.667

Gnomad AFR exome AF: 0.245

Gnomad AMR exome AF: 0.762

Gnomad ASJ exome AF: 0.668

Gnomad EAS exome AF: 0.627

Gnomad FIN exome AF: 0.778

Gnomad NFE exome AF: 0.710

Gnomad OTH exome AF: 0.672

GnomAD4 exome AF: 0.691 AC: 1000895 AN: 1449386 Hom.: 350510 Cov.: 34 AF XY: 0.688 AC XY: 495704 AN XY: 720124

African (AFR) AF: 0.236 AC: 7865 AN: 33358

American (AMR) AF: 0.756 AC: 32136 AN: 42532

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 17482 AN: 25888

East Asian (EAS) AF: 0.618 AC: 24349 AN: 39386

South Asian (SAS) AF: 0.572 AC: 48744 AN: 85146

European-Finnish (FIN) AF: 0.781 AC: 41220 AN: 52812

Middle Eastern (MID) AF: 0.614 AC: 3532 AN: 5750

European-Non Finnish (NFE) AF: 0.712 AC: 786266 AN: 1104540

Other (OTH) AF: 0.655 AC: 39301 AN: 59974

GnomAD4 genome AF: 0.581 AC: 88257 AN: 151966 Hom.: 28908 Cov.: 31 AF XY: 0.585 AC XY: 43436 AN XY: 74298

African (AFR) AF: 0.253 AC: 10491 AN: 41436

American (AMR) AF: 0.705 AC: 10755 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2333 AN: 3468

East Asian (EAS) AF: 0.621 AC: 3200 AN: 5150

South Asian (SAS) AF: 0.553 AC: 2660 AN: 4814

European-Finnish (FIN) AF: 0.773 AC: 8196 AN: 10604

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48472 AN: 67926

Other (OTH) AF: 0.605 AC: 1275 AN: 2106

Alfa AF: 0.669 Hom.: 19835

Bravo AF: 0.565

Asia WGS AF: 0.568 AC: 1977 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.9
DANN	Benign	0.72
PhyloP100		0.41
PromoterAI		-0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2293968; hg19: chr9-131587240; COSMIC: COSV63510028; COSMIC: COSV63510028;