rs747589966

Variant names:

• chr11-57302166-C-A
• rs747589966
• NM_033396.3:c.4742G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-57302166-C-A
• chr11-57302166-C-T

Variant summary

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

The NM_033396.3(TNKS1BP1):​c.4742G>T​(p.Arg1581Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,238 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1581H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TNKS1BP1 NM_033396.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 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.4742G>T	p.Arg1581Leu	missense_variant	Exon 8 of 12	ENST00000358252.8	NP_203754.2
TNKS1BP1	XM_006718725.4	c.4742G>T	p.Arg1581Leu	missense_variant	Exon 8 of 12		XP_006718788.1
TNKS1BP1	XM_047427785.1	c.2714G>T	p.Arg905Leu	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.4742G>T	p.Arg1581Leu	missense_variant	Exon 8 of 12	1	NM_033396.3	ENSP00000350990.3
TNKS1BP1	ENST00000532437.1	c.4742G>T	p.Arg1581Leu	missense_variant	Exon 7 of 11	1		ENSP00000437271.1
TNKS1BP1	ENST00000528882.5	n.*3103-2205G>T		intron_variant	Intron 6 of 6	5		ENSP00000431616.1
TNKS1BP1	ENST00000427750.2	n.1080G>T		non_coding_transcript_exon_variant	Exon 2 of 6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461238 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726940

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T;T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	.;D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.19
Sift	Uncertain	0.0020	D;D
Sift4G	Benign	0.10	T;T
Polyphen		1.0	D;D
Vest4		0.68
MutPred		0.33		Loss of methylation at R1581 (P = 0.0065);Loss of methylation at R1581 (P = 0.0065);
MVP		0.68
MPC		0.48
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.49
gMVP		0.45

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: rs747589966; hg19: chr11-57069640;