9-86303134-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_024617.4(TUT7):c.4046T>C(p.Ile1349Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TUT7 NM_024617.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.77

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 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=0.3020355).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUT7	NM_024617.4	c.4046T>C	p.Ile1349Thr	missense_variant	25/27	ENST00000375963.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUT7	ENST00000375963.8	c.4046T>C	p.Ile1349Thr	missense_variant	25/27	5	NM_024617.4	P1
TUT7	ENST00000375960.6	c.3338T>C	p.Ile1113Thr	missense_variant	18/20	1
TUT7	ENST00000277141.10	c.1913T>C	p.Ile638Thr	missense_variant	26/28	2
TUT7	ENST00000375957.5	c.746T>C	p.Ile249Thr	missense_variant	10/12	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.4046T>C (p.I1349T) alteration is located in exon 25 (coding exon 24) of the ZCCHC6 gene. This alteration results from a T to C substitution at nucleotide position 4046, causing the isoleucine (I) at amino acid position 1349 to be replaced by a threonine (T). 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	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
Cadd	Uncertain	24
Dann	Uncertain	0.99
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T;T;T;T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Uncertain	-0.072	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.2	D;D;D;D
REVEL	Uncertain	0.51
Sift	Benign	0.049	D;T;T;D
Sift4G	Uncertain	0.041	D;T;T;T
Polyphen		0.85, 0.89	.;P;.;P
Vest4		0.36
MutPred		0.47		.;.;.;Gain of disorder (P = 0.0342);
MVP		0.15
MPC		0.95
ClinPred		0.97	D
GERP RS		4.9
Varity_R		0.58
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr9-88918049;