chr8-9556210-A-G

Position:

• chr8-9556210-A-G

Variant summary

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

The NM_003747.3(TNKS):​c.271A>G​(p.Ser91Gly) 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. 15/21 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: TNKS NM_003747.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.18

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=0.09764826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNKS	NM_003747.3	c.271A>G	p.Ser91Gly	missense_variant	1/27	ENST00000310430.11	NP_003738.2
TNKS	XM_011543845.4	c.271A>G	p.Ser91Gly	missense_variant	1/28		XP_011542147.1
TNKS	XM_011543846.4	c.271A>G	p.Ser91Gly	missense_variant	1/27		XP_011542148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNKS	ENST00000310430.11	c.271A>G	p.Ser91Gly	missense_variant	1/27	1	NM_003747.3	ENSP00000311579	P1
TNKS	ENST00000517770.2	c.271A>G	p.Ser91Gly	missense_variant	1/28	4		ENSP00000428185
TNKS	ENST00000520408.5	c.271A>G	p.Ser91Gly	missense_variant	1/11	2		ENSP00000428299
TNKS	ENST00000522110.1	c.271A>G	p.Ser91Gly	missense_variant	1/1			ENSP00000430920

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

Apr 04, 2023

The c.271A>G (p.S91G) alteration is located in exon 1 (coding exon 1) of the TNKS gene. This alteration results from a A to G substitution at nucleotide position 271, causing the serine (S) at amino acid position 91 to be replaced by a glycine (G). 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	0.065
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.29	.;T;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.59	T;T;T
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.098	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	.;N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.18	N;N;N
REVEL	Benign	0.059
Sift	Uncertain	0.016	D;T;D
Sift4G	Benign	0.16	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.26
MutPred		0.18		Loss of stability (P = 0.0414);Loss of stability (P = 0.0414);Loss of stability (P = 0.0414);
MVP		0.40
MPC		0.34
ClinPred		0.29	T
GERP RS		3.9
Varity_R		0.12
gMVP		0.076

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: chr8-9413720;