11-57302155-C-G

Variant names:

• chr11-57302155-C-G
• NM_033396.3:c.4753G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_033396.3(TNKS1BP1):​c.4753G>C​(p.Ala1585Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 4.64

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.782

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNKS1BP1	NM_033396.3	c.4753G>C	p.Ala1585Pro	missense_variant	Exon 8 of 12	ENST00000358252.8	NP_203754.2
TNKS1BP1	XM_006718725.4	c.4753G>C	p.Ala1585Pro	missense_variant	Exon 8 of 12		XP_006718788.1
TNKS1BP1	XM_047427785.1	c.2725G>C	p.Ala909Pro	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.4753G>C	p.Ala1585Pro	missense_variant	Exon 8 of 12	1	NM_033396.3	ENSP00000350990.3
TNKS1BP1	ENST00000532437.1	c.4753G>C	p.Ala1585Pro	missense_variant	Exon 7 of 11	1		ENSP00000437271.1
TNKS1BP1	ENST00000528882.5	n.*3103-2194G>C		intron_variant	Intron 6 of 6	5		ENSP00000431616.1
TNKS1BP1	ENST00000427750.2	n.1091G>C		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

May 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4753G>C (p.A1585P) alteration is located in exon 8 (coding exon 7) of the TNKS1BP1 gene. This alteration results from a G to C substitution at nucleotide position 4753, causing the alanine (A) at amino acid position 1585 to be replaced by a proline (P). 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	0.53
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T;T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	.;T
M_CAP	Benign	0.059	D
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-4.4	D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.018	D;D
Polyphen		1.0	D;D
Vest4		0.81
MutPred		0.40		Loss of MoRF binding (P = 0.0577);Loss of MoRF binding (P = 0.0577);
MVP		0.77
MPC		0.49
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.82
gMVP		0.28

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: chr11-57069629;