NM_022830.3:c.2061C>G

Variant names:

• chr11-62575658-G-C
• rs34320415
• NM_022830.3:c.2061C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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. 15/21 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.83
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 25 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022830.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUT1	NM_022830.3	MANE Select	c.2061C>G	p.Asp687Glu	missense	Exon 9 of 9	NP_073741.3	Q9H6E5
	TUT1	NM_001367906.1		c.*475C>G		3_prime_UTR	Exon 9 of 9	NP_001354835.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUT1	ENST00000476907.6	TSL:1 MANE Select	c.2061C>G	p.Asp687Glu	missense	Exon 9 of 9	ENSP00000419607.1	Q9H6E5
	TUT1	ENST00000308436.11	TSL:1	c.2175C>G	p.Asp725Glu	missense	Exon 9 of 9	ENSP00000308000.7	F5H0R1
	ENSG00000255508	ENST00000496634.2	TSL:2	n.1475-750C>G		intron	N/A	ENSP00000456163.1	H3BRB1

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

GnomAD2 exomes AF: 0.00279 AC: 701 AN: 251456 AF XY: 0.00207

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 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

African (AFR) AF: 0.0389 AC: 1303 AN: 33480

American (AMR) AF: 0.00123 AC: 55 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5768

European-Non Finnish (NFE) AF: 0.0000576 AC: 64 AN: 1112010

Other (OTH) AF: 0.00200 AC: 121 AN: 60396

GnomAD4 genome AF: 0.00993 AC: 1512 AN: 152196 Hom.: 25 Cov.: 32 AF XY: 0.00964 AC XY: 717 AN XY: 74410

African (AFR) AF: 0.0347 AC: 1439 AN: 41516

American (AMR) AF: 0.00288 AC: 44 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68002

Other (OTH) AF: 0.00710 AC: 15 AN: 2112

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		-1.8
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.036
Sift	Benign	0.59	T
Sift4G	Benign	0.66	T
Polyphen		0.0010	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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs34320415; hg19: chr11-62343130;