9-86303162-G-C

Position:

• chr9-86303162-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_024617.4(TUT7):​c.4018C>G​(p.Leu1340Val) 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: TUT7 NM_024617.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.904

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 1 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=0.13843387).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUT7	NM_024617.4	c.4018C>G	p.Leu1340Val	missense_variant	25/27	ENST00000375963.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUT7	ENST00000375963.8	c.4018C>G	p.Leu1340Val	missense_variant	25/27	5	NM_024617.4	P1
TUT7	ENST00000375960.6	c.3310C>G	p.Leu1104Val	missense_variant	18/20	1
TUT7	ENST00000277141.10	c.1885C>G	p.Leu629Val	missense_variant	26/28	2
TUT7	ENST00000375957.5	c.718C>G	p.Leu240Val	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

Jan 03, 2024

The c.4018C>G (p.L1340V) alteration is located in exon 25 (coding exon 24) of the ZCCHC6 gene. This alteration results from a C to G substitution at nucleotide position 4018, causing the leucine (L) at amino acid position 1340 to be replaced by a valine (V). 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	0.22
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Benign	0.080
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Uncertain	-0.24	T
MutationTaster	Benign	0.83	D;D;D;D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.7	N;N;N;N
REVEL	Benign	0.24
Sift	Benign	0.076	T;T;T;T
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.54, 0.76	.;P;.;P
Vest4		0.27
MutPred		0.32		.;.;.;Gain of sheet (P = 0.1208);
MVP		0.27
MPC		0.79
ClinPred		0.75	D
GERP RS		3.0
Varity_R		0.36
gMVP		0.36

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: chr9-88918077;