11-57302146-T-A

Variant names:

• chr11-57302146-T-A
• rs1855534215
• NM_033396.3:c.4762A>T

Variant summary

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

The NM_033396.3(TNKS1BP1):​c.4762A>T​(p.Ile1588Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNKS1BP1 NM_033396.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18

Genes affected

TNKS1BP1 (HGNC:19081): (tankyrase 1 binding protein 1) Enables ankyrin repeat binding activity and enzyme binding activity. Involved in cellular response to ionizing radiation; double-strand break repair; and positive regulation of protein phosphorylation. Located in several cellular components, including actin cytoskeleton; adherens junction; and heterochromatin. Part of CCR4-NOT complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNKS1BP1	NM_033396.3	c.4762A>T	p.Ile1588Phe	missense_variant	Exon 8 of 12	ENST00000358252.8	NP_203754.2
TNKS1BP1	XM_006718725.4	c.4762A>T	p.Ile1588Phe	missense_variant	Exon 8 of 12		XP_006718788.1
TNKS1BP1	XM_047427785.1	c.2734A>T	p.Ile912Phe	missense_variant	Exon 4 of 8		XP_047283741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNKS1BP1	ENST00000358252.8	c.4762A>T	p.Ile1588Phe	missense_variant	Exon 8 of 12	1	NM_033396.3	ENSP00000350990.3
TNKS1BP1	ENST00000532437.1	c.4762A>T	p.Ile1588Phe	missense_variant	Exon 7 of 11	1		ENSP00000437271.1
TNKS1BP1	ENST00000528882.5	n.*3103-2185A>T		intron_variant	Intron 6 of 6	5		ENSP00000431616.1
TNKS1BP1	ENST00000427750.2	n.1100A>T		non_coding_transcript_exon_variant	Exon 2 of 6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4762A>T (p.I1588F) alteration is located in exon 8 (coding exon 7) of the TNKS1BP1 gene. This alteration results from a A to T substitution at nucleotide position 4762, causing the isoleucine (I) at amino acid position 1588 to be replaced by a phenylalanine (F). 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	0.35
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.84	.;T
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.90	L;L
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0030	D;D
Sift4G	Benign	0.17	T;T
Polyphen		1.0	D;D
Vest4		0.68
MutPred		0.23		Loss of catalytic residue at P1590 (P = 0.0306);Loss of catalytic residue at P1590 (P = 0.0306);
MVP		0.70
MPC		0.54
ClinPred		0.77	D
GERP RS		4.1
Varity_R		0.12
gMVP		0.18

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: rs1855534215; hg19: chr11-57069620;