9-128823750-C-T

Variant names:

• chr9-128823750-C-T
• rs145802443
• NM_016390.4:c.1059G>A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_016390.4(SPOUT1):​c.1059G>A​(p.Thr353Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,601,298 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0015 (4 hom.)
• Consequence: SPOUT1 NM_016390.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -7.07

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]

ENSG00000286112 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 9-128823750-C-T is Benign according to our data. Variant chr9-128823750-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3770570.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-7.07 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00172 (262/152288) while in subpopulation AMR AF= 0.00235 (36/15288). AF 95% confidence interval is 0.00175. There are 0 homozygotes in gnomad4. There are 138 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPOUT1	NM_016390.4	c.1059G>A	p.Thr353Thr	synonymous_variant	Exon 11 of 12	ENST00000361256.10	NP_057474.2
KYAT1-SPOUT1	NM_001414398.1	c.2406G>A	p.Thr802Thr	synonymous_variant	Exon 22 of 23		NP_001401327.1
KYAT1-SPOUT1	NR_182310.1	n.3002G>A		non_coding_transcript_exon_variant	Exon 24 of 25
KYAT1-SPOUT1	NR_182311.1	n.2970G>A		non_coding_transcript_exon_variant	Exon 24 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPOUT1	ENST00000361256.10	c.1059G>A	p.Thr353Thr	synonymous_variant	Exon 11 of 12	1	NM_016390.4	ENSP00000354812.5
ENSG00000286112	ENST00000651925	c.*2098G>A		3_prime_UTR_variant	Exon 28 of 29			ENSP00000498386.1
SPOUT1	ENST00000467582.1	c.155+322G>A		intron_variant	Intron 2 of 2	2		ENSP00000473640.1
SPOUT1	ENST00000480366.1	n.622G>A		non_coding_transcript_exon_variant	Exon 5 of 6	2

Frequencies

GnomAD3 genomes AF: 0.00172 AC: 262 AN: 152170 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00696

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00182

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00160 AC: 362 AN: 226906 Hom.: 1 AF XY: 0.00148 AC XY: 182 AN XY: 122714

Gnomad AFR exome AF: 0.0000708

Gnomad AMR exome AF: 0.00105

Gnomad ASJ exome AF: 0.00676

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000609

Gnomad FIN exome AF: 0.00653

Gnomad NFE exome AF: 0.00107

Gnomad OTH exome AF: 0.00255

GnomAD4 exome AF: 0.00154 AC: 2229 AN: 1449010 Hom.: 4 Cov.: 35 AF XY: 0.00154 AC XY: 1111 AN XY: 719614

Gnomad4 AFR exome AF: 0.000150

Gnomad4 AMR exome AF: 0.00104

Gnomad4 ASJ exome AF: 0.00728

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000727

Gnomad4 FIN exome AF: 0.00723

Gnomad4 NFE exome AF: 0.00133

Gnomad4 OTH exome AF: 0.00152

GnomAD4 genome AF: 0.00172 AC: 262 AN: 152288 Hom.: 0 Cov.: 31 AF XY: 0.00185 AC XY: 138 AN XY: 74468

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00696

Gnomad4 NFE AF: 0.00182

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00205 Hom.: 1

Bravo AF: 0.00116

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SPOUT1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.049
DANN	Benign	0.91

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

Other links and lift over

dbSNP: rs145802443; hg19: chr9-131586029;