9-86301383-T-G

Variant names:

• chr9-86301383-T-G
• rs1826876367
• NM_024617.4:c.4313A>C

Variant summary

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

The NM_024617.4(TUT7):​c.4313A>C​(p.Glu1438Ala) 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. 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: 3.52

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
• BP4: Computational evidence support a benign effect (MetaRNN=0.31286377).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUT7	NM_024617.4	c.4313A>C	p.Glu1438Ala	missense_variant	Exon 26 of 27	ENST00000375963.8	NP_078893.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUT7	ENST00000375963.8	c.4313A>C	p.Glu1438Ala	missense_variant	Exon 26 of 27	5	NM_024617.4	ENSP00000365130.3
TUT7	ENST00000375960.6	c.3605A>C	p.Glu1202Ala	missense_variant	Exon 19 of 20	1		ENSP00000365127.2
TUT7	ENST00000277141.10	c.2180A>C	p.Glu727Ala	missense_variant	Exon 27 of 28	2		ENSP00000277141.6
TUT7	ENST00000375957.5	c.1013A>C	p.Glu338Ala	missense_variant	Exon 11 of 12	2		ENSP00000365124.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 15, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4313A>C (p.E1438A) alteration is located in exon 26 (coding exon 25) of the ZCCHC6 gene. This alteration results from a A to C substitution at nucleotide position 4313, causing the glutamic acid (E) at amino acid position 1438 to be replaced by an alanine (A). 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	Uncertain	0.44
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	.;.;T;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.31	T;T;T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.3	.;.;.;M
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.7	D;D;D;D
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D
Polyphen		1.0, 0.42	.;D;.;B
Vest4		0.51
MutPred		0.20		.;.;.;Loss of solvent accessibility (P = 0.0224);
MVP		0.14
MPC		1.6
ClinPred		0.94	D
GERP RS		5.4
Varity_R		0.37
gMVP		0.32

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

LitVar

Other links and lift over

dbSNP: rs1826876367; hg19: chr9-88916298;