9-86323199-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2 BP4_Strong BP6_Moderate BS1 BS2

The NM_024617.4(TUT7):c.2551G>A(p.Asp851Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000546 in 1,614,120 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00077 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00052 (2 hom.)
• Consequence: TUT7 NM_024617.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.28

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 Benign. Variant got -13 ACMG points.

• PP2: Missense variant where missense usually causes diseases, TUT7
• BP4: Computational evidence support a benign effect (MetaRNN=0.0027566254).
• BP6: Variant 9-86323199-C-T is Benign according to our data. Variant chr9-86323199-C-T is described in ClinVar as [Benign]. Clinvar id is 726973.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000768 (117/152292) while in subpopulation EAS AF= 0.0197 (102/5178). AF 95% confidence interval is 0.0166. There are 0 homozygotes in gnomad4. There are 69 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUT7	NM_024617.4	c.2551G>A	p.Asp851Asn	missense_variant	13/27	ENST00000375963.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUT7	ENST00000375963.8	c.2551G>A	p.Asp851Asn	missense_variant	13/27	5	NM_024617.4	P1
TUT7	ENST00000375960.6	c.2182G>A	p.Asp728Asn	missense_variant	9/20	1
TUT7	ENST00000277141.10	c.418G>A	p.Asp140Asn	missense_variant	14/28	2

Frequencies

GnomAD3 genomes AF: 0.000769 AC: 117 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0197

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.00149 AC: 373 AN: 251104 Hom.: 3 AF XY: 0.00144 AC XY: 196 AN XY: 135726

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0178

Gnomad SAS exome AF: 0.00118

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000981

GnomAD4 exome AF: 0.000523 AC: 764 AN: 1461828 Hom.: 2 Cov.: 33 AF XY: 0.000528 AC XY: 384 AN XY: 727202

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000895

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0146

Gnomad4 SAS exome AF: 0.00123

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000378

Gnomad4 OTH exome AF: 0.000497

GnomAD4 genome AF: 0.000768 AC: 117 AN: 152292 Hom.: 0 Cov.: 32 AF XY: 0.000927 AC XY: 69 AN XY: 74462

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0197

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000984 Hom.: 3

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.00128 AC: 156

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.51
Cadd	Benign	8.7
Dann	Uncertain	1.0
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.72	T;T;T
MetaRNN	Benign	0.0028	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.93	N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.55	N;N;N
REVEL	Benign	0.046
Sift	Uncertain	0.0080	D;D;T
Sift4G	Benign	0.14	T;T;T
Polyphen		0.42, 0.51	.;B;P
Vest4		0.13
MVP		0.11
MPC		0.22
ClinPred		0.021	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.063
gMVP		0.069

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: rs139212809; hg19: chr9-88938114; COSMIC: COSV52898158; COSMIC: COSV52898158;