11-62575658-G-C

Position:

• chr11-62575658-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000476907.6(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 ENST00000476907.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.83

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]

ENSG00000255508 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
TUT1	NM_022830.3	c.2061C>G	p.Asp687Glu	missense_variant	9/9	ENST00000476907.6	NP_073741.3
TUT1	NM_001367906.1	c.*475C>G		3_prime_UTR_variant	9/9		NP_001354835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUT1	ENST00000476907.6	c.2061C>G	p.Asp687Glu	missense_variant	9/9	1	NM_022830.3	ENSP00000419607.1
ENSG00000255508	ENST00000496634.2	n.1475-750C>G		intron_variant		2		ENSP00000456163.1

Frequencies

GnomAD3 genomes AF: 0.00992 AC: 1509 AN: 152078 Hom.: 25 Cov.: 32

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.: 12 AF XY: 0.00207 AC XY: 282 AN XY: 135910

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.: 28 Cov.: 31 AF XY: 0.000902 AC XY: 656 AN XY: 727244

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.: 25 Cov.: 32 AF XY: 0.00964 AC XY: 717 AN XY: 74410

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.: 2

Bravo AF: 0.0112

ESP6500AA AF: 0.0352 AC: 155

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00352 AC: 428

Asia WGS AF: 0.00231 AC: 9 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 24, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.73	T
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	N
LIST_S2	Benign	0.47	T;T
MetaRNN	Benign	0.0018	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	.;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.29	T
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	T
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

Other links and lift over

dbSNP: rs34320415; hg19: chr11-62343130;