9-128822790-A-C

Variant names:

• chr9-128822790-A-C
• rs2280843
• NM_016390.4:c.1106T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016390.4(SPOUT1):​c.1106T>G​(p.Ile369Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I369T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SPOUT1 NM_016390.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104
• Publications: 40 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]

KYAT1 (HGNC:):

ENDOG (HGNC:3346): (endonuclease G) The protein encoded by this gene is a nuclear encoded endonuclease that is localized in the mitochondrion. The encoded protein is widely distributed among animals and cleaves DNA at GC tracts. This protein is capable of generating the RNA primers required by DNA polymerase gamma to initiate replication of mitochondrial DNA. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029504985).

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.1106T>G	p.Ile369Ser	missense	Exon 12 of 12	NP_057474.2
	KYAT1-SPOUT1	NM_001414398.1		c.2453T>G	p.Ile818Ser	missense	Exon 23 of 23	NP_001401327.1
	KYAT1-SPOUT1	NR_182310.1		n.3049T>G		non_coding_transcript_exon	Exon 25 of 25

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPOUT1	ENST00000361256.10	TSL:1 MANE Select	c.1106T>G	p.Ile369Ser	missense	Exon 12 of 12	ENSP00000354812.5	Q5T280
	KYAT1	ENST00000651925.1		c.*2145T>G		3_prime_UTR	Exon 29 of 29	ENSP00000498386.1	A0A494C066
	SPOUT1	ENST00000965412.1		c.1148T>G	p.Ile383Ser	missense	Exon 12 of 12	ENSP00000635471.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.3
DANN	Benign	0.72
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.10
PROVEAN	Benign	1.1	N
REVEL	Benign	0.040
Sift	Benign	0.89	T
Sift4G	Benign	0.79	T
Polyphen		0.0	B
Vest4		0.048
MutPred		0.23		Gain of disorder (P = 0.0018)
MVP		0.12
MPC		0.59
ClinPred		0.038	T
GERP RS		-0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.043
gMVP		0.46
Mutation Taster		=97/3	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: rs2280843; hg19: chr9-131585069;