8-9556010-C-T

Position:

• chr8-9556010-C-T

Variant summary

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

The NM_003747.3(TNKS):​c.71C>T​(p.Ala24Val) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TNKS NM_003747.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.61

Genes affected

TNKS (HGNC:11941): (tankyrase) Enables histone binding activity; pentosyltransferase activity; and zinc ion binding activity. Involved in several processes, including negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric; protein ADP-ribosylation; and regulation of nucleobase-containing compound metabolic process. Acts upstream of or within peptidyl-serine phosphorylation; peptidyl-threonine phosphorylation; and protein ADP-ribosylation. Located in several cellular components, including chromosome, telomeric region; mitotic spindle pole; and nucleus. [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=0.10961118).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNKS	NM_003747.3	c.71C>T	p.Ala24Val	missense_variant	1/27	ENST00000310430.11
TNKS	XM_011543845.4	c.71C>T	p.Ala24Val	missense_variant	1/28
TNKS	XM_011543846.4	c.71C>T	p.Ala24Val	missense_variant	1/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNKS	ENST00000310430.11	c.71C>T	p.Ala24Val	missense_variant	1/27	1	NM_003747.3	P1
TNKS	ENST00000517770.2	c.71C>T	p.Ala24Val	missense_variant	1/28	4
TNKS	ENST00000520408.5	c.71C>T	p.Ala24Val	missense_variant	1/11	2
TNKS	ENST00000522110.1	c.71C>T	p.Ala24Val	missense_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Dec 19, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	.;T;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Uncertain	0.099	D
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	.;N;.
MutationTaster	Benign	0.94	N;N;N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.010	N;N;N
REVEL	Benign	0.069
Sift	Uncertain	0.0040	D;D;D
Sift4G	Benign	0.80	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.42
MutPred		0.28		Loss of glycosylation at P22 (P = 0.0724);Loss of glycosylation at P22 (P = 0.0724);Loss of glycosylation at P22 (P = 0.0724);
MVP		0.19
MPC		0.37
ClinPred		0.56	D
GERP RS		4.0
Varity_R		0.13
gMVP		0.066

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: chr8-9413520;