9-86308580-T-G

Variant names:

• chr9-86308580-T-G
• NM_024617.4:c.3687A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024617.4(TUT7):​c.3687A>C​(p.Lys1229Asn) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TUT7 NM_024617.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.90

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20885113).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUT7	NM_024617.4	c.3687A>C	p.Lys1229Asn	missense_variant	Exon 22 of 27	ENST00000375963.8	NP_078893.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUT7	ENST00000375963.8	c.3687A>C	p.Lys1229Asn	missense_variant	Exon 22 of 27	5	NM_024617.4	ENSP00000365130.3
TUT7	ENST00000375960.6	c.2979A>C	p.Lys993Asn	missense_variant	Exon 15 of 20	1		ENSP00000365127.2
TUT7	ENST00000277141.10	c.1554A>C	p.Lys518Asn	missense_variant	Exon 23 of 28	2		ENSP00000277141.6
TUT7	ENST00000375957.5	c.387A>C	p.Lys129Asn	missense_variant	Exon 7 of 12	2		ENSP00000365124.1

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

Jan 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3687A>C (p.K1229N) alteration is located in exon 22 (coding exon 21) of the ZCCHC6 gene. This alteration results from a A to C substitution at nucleotide position 3687, causing the lysine (K) at amino acid position 1229 to be replaced by an asparagine (N). 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	0.26
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.077	.;.;T;T
Eigen	Benign	0.072
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	T;T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.3	.;.;.;M
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.7	D;D;D;D
REVEL	Benign	0.063
Sift	Uncertain	0.013	D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D
Polyphen		0.83, 0.088	.;P;.;B
Vest4		0.19
MutPred		0.45		.;.;.;Loss of ubiquitination at K1229 (P = 0.0116);
MVP		0.16
MPC		0.78
ClinPred		0.91	D
GERP RS		3.0
Varity_R		0.31
gMVP		0.72

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: chr9-88923495;