9-128823750-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate 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
• Publications: 0 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.112).
• 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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016390.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPOUT1	NM_016390.4	MANE Select	c.1059G>A	p.Thr353Thr	synonymous	Exon 11 of 12	NP_057474.2
	KYAT1-SPOUT1	NM_001414398.1		c.2406G>A	p.Thr802Thr	synonymous	Exon 22 of 23	NP_001401327.1
	KYAT1-SPOUT1	NR_182310.1		n.3002G>A		non_coding_transcript_exon	Exon 24 of 25

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPOUT1	ENST00000361256.10	TSL:1 MANE Select	c.1059G>A	p.Thr353Thr	synonymous	Exon 11 of 12	ENSP00000354812.5	Q5T280
	KYAT1	ENST00000651925.1		c.*2098G>A		3_prime_UTR	Exon 28 of 29	ENSP00000498386.1	A0A494C066
	SPOUT1	ENST00000965412.1		c.1101G>A	p.Thr367Thr	synonymous	Exon 11 of 12	ENSP00000635471.1

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

GnomAD2 exomes AF: 0.00160 AC: 362 AN: 226906 AF XY: 0.00148

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 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

African (AFR) AF: 0.000150 AC: 5 AN: 33400

American (AMR) AF: 0.00104 AC: 44 AN: 42282

Ashkenazi Jewish (ASJ) AF: 0.00728 AC: 186 AN: 25544

East Asian (EAS) AF: 0.00 AC: 0 AN: 39244

South Asian (SAS) AF: 0.000727 AC: 61 AN: 83900

European-Finnish (FIN) AF: 0.00723 AC: 373 AN: 51566

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5742

European-Non Finnish (NFE) AF: 0.00133 AC: 1468 AN: 1107450

Other (OTH) AF: 0.00152 AC: 91 AN: 59882

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

African (AFR) AF: 0.0000962 AC: 4 AN: 41566

American (AMR) AF: 0.00235 AC: 36 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00696 AC: 74 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00182 AC: 124 AN: 68006

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00205 Hom.: 1

Bravo AF: 0.00116

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.049
DANN	Benign	0.91
PhyloP100		-7.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs145802443; hg19: chr9-131586029;