11-62575658-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_022830.3(TUT1):c.2061C>G(p.Asp687Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,614,076 control chromosomes in the GnomAD database, including 53 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 0.0099 ( 25 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 28 hom. )

Consequence

TUT1
NM_022830.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.83

Variant links:

Genes affected

TUT1 (HGNC:26184): (terminal uridylyl transferase 1, U6 snRNA-specific) This gene encodes a nucleotidyl transferase that functions as both a terminal uridylyltransferase and a nuclear poly(A) polymerase. The encoded enzyme specifically adds and removes nucleotides from the 3' end of small nuclear RNAs and select mRNAs and may function in controlling gene expression and cell proliferation.[provided by RefSeq, Apr 2009]

TUT1 links:

ENSG00000255508 (HGNC:):

ENSG00000255508 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017508566).

BP6

Variant 11-62575658-G-C is Benign according to our data. Variant chr11-62575658-G-C is described in ClinVar as [Benign]. Clinvar id is 710010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00993 (1512/152196) while in subpopulation AFR AF= 0.0347 (1439/41516). AF 95% confidence interval is 0.0332. There are 25 homozygotes in gnomad4. There are 717 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUT1	NM_022830.3 link	c.2061C>G	p.Asp687Glu	missense_variant	Exon 9 of 9	ENST00000476907.6	NP_073741.3	Q9H6E5A0A0A8K9B1F5H0R1
TUT1	NM_001367906.1 link	c.*475C>G		3_prime_UTR_variant	Exon 9 of 9		NP_001354835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUT1	ENST00000476907.6 link	c.2061C>G	p.Asp687Glu	missense_variant	Exon 9 of 9	1	NM_022830.3	ENSP00000419607.1		Q9H6E5
ENSG00000255508	ENST00000496634.2 link	n.1475-750C>G		intron_variant	Intron 8 of 16	2		ENSP00000456163.1		H3BRB1

Frequencies

GnomAD3 genomes

AF:

0.00992

AC:

1509

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0347

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00279

AC:

701

AN:

251456

Hom.:

AF XY:

0.00207

AC XY:

282

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.0390

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00107

AC:

1570

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000902

AC XY:

656

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0389

Gnomad4 AMR exome

AF:

0.00123

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000576

Gnomad4 OTH exome

AF:

0.00200

GnomAD4 genome

AF:

0.00993

AC:

1512

AN:

152196

Hom.:

Cov.:

AF XY:

0.00964

AC XY:

717

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0347

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00317

Hom.:

Bravo

AF:

0.0112

ESP6500AA

AF:

0.0352

AC:

155

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00352

AC:

428

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 24, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.0010

DANN

Benign

0.50

DEOGEN2

Benign

0.017

.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.47

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

.;L

PrimateAI

Benign

0.29

PROVEAN

Benign

0.070

N;N

REVEL

Benign

0.036

Sift

Benign

0.59

T;T

Sift4G

Benign

0.66

T;T

Polyphen

0.0010

B;B

Vest4

0.052

MutPred

0.15

Gain of helix (P = 0.0325);.;

MVP

0.19

MPC

0.20

ClinPred

0.0019

GERP RS

-10

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.039

gMVP

0.055

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