rs2293968

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

KYAT1-SPOUT1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SPOUT1	NM_016390.4	c.712+16C>T		intron_variant		ENST00000361256.10
KYAT1-SPOUT1	NR_182311.1	n.2623+16C>T		intron_variant, non_coding_transcript_variant
KYAT1-SPOUT1	NM_001414398.1	c.2059+16C>T		intron_variant
KYAT1-SPOUT1	NR_182310.1	n.2655+16C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPOUT1	ENST00000361256.10	c.712+16C>T		intron_variant		1	NM_016390.4	P1
SPOUT1	ENST00000480366.1	n.275+16C>T		intron_variant, non_coding_transcript_variant		2

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

GnomAD3 exomes AF: 0.667 AC: 154877 AN: 232154 Hom.: 53451 AF XY: 0.667 AC XY: 83692 AN XY: 125458

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 SAS exome AF: 0.570

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

Gnomad4 AFR exome AF: 0.236

Gnomad4 AMR exome AF: 0.756

Gnomad4 ASJ exome AF: 0.675

Gnomad4 EAS exome AF: 0.618

Gnomad4 SAS exome AF: 0.572

Gnomad4 FIN exome AF: 0.781

Gnomad4 NFE exome AF: 0.712

Gnomad4 OTH exome AF: 0.655

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

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.705

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.714

Gnomad4 OTH AF: 0.605

Alfa AF: 0.672 Hom.: 17982

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

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