11-62575344-C-T

Variant names:

• chr11-62575344-C-T
• NM_022830.3:c.2375G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022830.3(TUT1):​c.2375G>A​(p.Gly792Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TUT1 NM_022830.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.956

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036047816).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUT1	NM_022830.3	c.2375G>A	p.Gly792Glu	missense_variant	Exon 9 of 9	ENST00000476907.6	NP_073741.3
TUT1	NM_001367906.1	c.*789G>A		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	c.2375G>A	p.Gly792Glu	missense_variant	Exon 9 of 9	1	NM_022830.3	ENSP00000419607.1
ENSG00000255508	ENST00000496634.2	n.1475-436G>A		intron_variant	Intron 8 of 16	2		ENSP00000456163.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2489G>A (p.G830E) alteration is located in exon 9 (coding exon 9) of the TUT1 gene. This alteration results from a G to A substitution at nucleotide position 2489, causing the glycine (G) at amino acid position 830 to be replaced by a glutamic acid (E). 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	0.096
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.45
DANN	Benign	0.74
DEOGEN2	Benign	0.018	.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.036	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.14	.;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.25	N;N
REVEL	Benign	0.020
Sift	Benign	0.59	T;T
Sift4G	Benign	0.71	T;T
Polyphen		0.0	B;B
Vest4		0.097
MutPred		0.23		Gain of solvent accessibility (P = 0.0068);.;
MVP		0.099
MPC		0.28
ClinPred		0.065	T
GERP RS		-0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-62342816;