8-9556040-C-T

Variant names:

• chr8-9556040-C-T
• rs371322654
• NM_003747.3:c.101C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003747.3(TNKS):​c.101C>T​(p.Pro34Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,459,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. P34Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TNKS NM_003747.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.48
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23089522).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003747.3. 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
	TNKS	NM_003747.3	MANE Select	c.101C>T	p.Pro34Leu	missense	Exon 1 of 27	NP_003738.2	O95271-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNKS	ENST00000310430.11	TSL:1 MANE Select	c.101C>T	p.Pro34Leu	missense	Exon 1 of 27	ENSP00000311579.6	O95271-1
	TNKS	ENST00000517770.2	TSL:4	c.101C>T	p.Pro34Leu	missense	Exon 1 of 28	ENSP00000428185.2	H0YAW5
	TNKS	ENST00000885812.1		c.101C>T	p.Pro34Leu	missense	Exon 1 of 27	ENSP00000555871.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000417 AC: 1 AN: 239732 AF XY: 0.00000762

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459344 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 725998

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.0000224 AC: 1 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26024

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111432

Other (OTH) AF: 0.00 AC: 0 AN: 60258

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.86	D
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.5
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.30	T
Polyphen		0.91	P
Vest4		0.49
MutPred		0.28		Loss of glycosylation at P34 (P = 6e-04)
MVP		0.20
MPC		0.38
ClinPred		0.62	D
GERP RS		4.8
PromoterAI		0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.37
gMVP		0.074
Mutation Taster		=89/11	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: rs371322654; hg19: chr8-9413550;