11-57301029-G-A

Variant names:

• chr11-57301029-G-A
• rs766053075
• NM_033396.3:c.4984C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_033396.3(TNKS1BP1):​c.4984C>T​(p.Pro1662Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000807 in 1,611,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: TNKS1BP1 NM_033396.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.733
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012159735).
• BP6: Variant 11-57301029-G-A is Benign according to our data. Variant chr11-57301029-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3327607.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033396.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNKS1BP1	NM_033396.3	MANE Select	c.4984C>T	p.Pro1662Ser	missense	Exon 10 of 12	NP_203754.2	Q9C0C2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNKS1BP1	ENST00000358252.8	TSL:1 MANE Select	c.4984C>T	p.Pro1662Ser	missense	Exon 10 of 12	ENSP00000350990.3	Q9C0C2-1
	TNKS1BP1	ENST00000532437.1	TSL:1	c.4984C>T	p.Pro1662Ser	missense	Exon 9 of 11	ENSP00000437271.1	Q9C0C2-1
	TNKS1BP1	ENST00000528882.5	TSL:5	n.*3103-1068C>T		intron	N/A	ENSP00000431616.1	E9PKK0

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152076 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000324 AC: 8 AN: 247114 AF XY: 0.0000374

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000441

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000754 AC: 11 AN: 1459196 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 725526

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39612

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5524

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110504

Other (OTH) AF: 0.00 AC: 0 AN: 60262

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152076 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74280

African (AFR) AF: 0.00 AC: 0 AN: 41392

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.057
DANN	Benign	0.57
DEOGEN2	Benign	0.00053	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-0.73
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.82	N
REVEL	Benign	0.037
Sift	Benign	1.0	T
Sift4G	Benign	0.74	T
Polyphen		0.0	B
Vest4		0.21
MutPred		0.18		Gain of phosphorylation at P1662 (P = 0.0031)
MVP		0.12
MPC		0.076
ClinPred		0.0093	T
GERP RS		-6.6
Varity_R		0.018
gMVP		0.26
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs766053075; hg19: chr11-57068503;