chr9-86310725-A-C

Variant names:

• chr9-86310725-A-C
• rs753140997
• NM_024617.4:c.3359T>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_024617.4(TUT7):​c.3359T>G​(p.Ile1120Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TUT7 NM_024617.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.95

Genes affected

TUT7 (HGNC:25817): (terminal uridylyl transferase 7) Enables RNA uridylyltransferase activity and miRNA binding activity. Involved in RNA metabolic process and negative regulation of transposition, RNA-mediated. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.934

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUT7	NM_024617.4	c.3359T>G	p.Ile1120Ser	missense_variant	Exon 18 of 27	ENST00000375963.8	NP_078893.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUT7	ENST00000375963.8	c.3359T>G	p.Ile1120Ser	missense_variant	Exon 18 of 27	5	NM_024617.4	ENSP00000365130.3
TUT7	ENST00000375960.6	c.2651T>G	p.Ile884Ser	missense_variant	Exon 11 of 20	1		ENSP00000365127.2
TUT7	ENST00000277141.10	c.1226T>G	p.Ile409Ser	missense_variant	Exon 19 of 28	2		ENSP00000277141.6
TUT7	ENST00000375957.5	c.173T>G	p.Ile58Ser	missense_variant	Exon 4 of 12	2		ENSP00000365124.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251260 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135820

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455082 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 724336

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	.;.;T;T
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D;D
M_CAP	Benign	0.076	D
MetaRNN	Pathogenic	0.93	D;D;D;D
MetaSVM	Uncertain	0.15	D
MutationAssessor	Pathogenic	3.7	.;.;.;H
PrimateAI	Pathogenic	0.80	D
PROVEAN	Pathogenic	-5.8	D;D;D;D
REVEL	Pathogenic	0.77
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0, 1.0	.;D;.;D
Vest4		0.96
MutPred		0.84		.;.;.;Gain of disorder (P = 0.003);
MVP		0.61
MPC		2.0
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.94
gMVP		0.99

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: rs753140997; hg19: chr9-88925640;