8-9556526-C-G

Variant summary

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

The NM_003747.3(TNKS):c.587C>G(p.Ser196Cys) 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: TNKS NM_003747.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.68

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3664745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNKS	NM_003747.3	c.587C>G	p.Ser196Cys	missense_variant	1/27	ENST00000310430.11
TNKS	XM_011543845.4	c.587C>G	p.Ser196Cys	missense_variant	1/28
TNKS	XM_011543846.4	c.587C>G	p.Ser196Cys	missense_variant	1/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNKS	ENST00000310430.11	c.587C>G	p.Ser196Cys	missense_variant	1/27	1	NM_003747.3	P1
TNKS	ENST00000517770.2	c.587C>G	p.Ser196Cys	missense_variant	1/28	4
TNKS	ENST00000520408.5	c.587C>G	p.Ser196Cys	missense_variant	1/11	2
TNKS	ENST00000522110.1	c.587C>G	p.Ser196Cys	missense_variant	1/1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2021

The c.587C>G (p.S196C) alteration is located in exon 1 (coding exon 1) of the TNKS gene. This alteration results from a C to G substitution at nucleotide position 587, causing the serine (S) at amino acid position 196 to be replaced by a cysteine (C). 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	0.12
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
Cadd	Pathogenic	29
Dann	Uncertain	0.99
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.20
Sift	Uncertain	0.016	D;T;D
Sift4G	Uncertain	0.018	D;D;D
Polyphen		1.0	D;P;.
Vest4		0.53
MutPred		0.40		Loss of disorder (P = 0.0312);Loss of disorder (P = 0.0312);Loss of disorder (P = 0.0312);
MVP		0.23
MPC		0.96
ClinPred		0.98	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.34
gMVP		0.31

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: chr8-9414036;