Variant 9-86301386-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong

The NM_024617.4(TUT7):c.4310T>C(p.Val1437Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,613,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

TUT7
NM_024617.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.09

Variant links:

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]

TUT7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, TUT7

BP4

Computational evidence support a benign effect (MetaRNN=0.0053705275).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUT7	NM_024617.4 linkuse as main transcript	c.4310T>C	p.Val1437Ala	missense_variant	26/27	ENST00000375963.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUT7	ENST00000375963.8 linkuse as main transcript	c.4310T>C	p.Val1437Ala	missense_variant	26/27	5	NM_024617.4	P1	Q5VYS8-1
TUT7	ENST00000375960.6 linkuse as main transcript	c.3602T>C	p.Val1201Ala	missense_variant	19/20	1			Q5VYS8-4
TUT7	ENST00000277141.10 linkuse as main transcript	c.2177T>C	p.Val726Ala	missense_variant	27/28	2
TUT7	ENST00000375957.5 linkuse as main transcript	c.1010T>C	p.Val337Ala	missense_variant	11/12	2

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151906

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000135

AC:

AN:

251302

Hom.:

AF XY:

0.000132

AC XY:

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00169

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000267

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000907

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152024

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00136

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

The c.4310T>C (p.V1437A) alteration is located in exon 26 (coding exon 25) of the ZCCHC6 gene. This alteration results from a T to C substitution at nucleotide position 4310, causing the valine (V) at amino acid position 1437 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.63

CADD

Benign

9.1

DANN

Benign

0.87

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.71

T;T;T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.0054

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.40

N;N;N;N

REVEL

Benign

0.039

Sift

Benign

0.33

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0010, 0.0

.;B;.;B

Vest4

0.055

MutPred

0.25

.;.;.;Gain of glycosylation at P1436 (P = 0.0631);

MVP

0.10

MPC

0.78

ClinPred

0.010

GERP RS

1.8

Varity_R

0.020

gMVP

0.16

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over