NM_003747.3:c.994+20514T>C

Variant names:

• chr8-9636191-T-C
• rs11994018
• NM_003747.3:c.994+20514T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003747.3(TNKS):​c.994+20514T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,188 control chromosomes in the GnomAD database, including 1,896 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (1896 hom., cov: 32)
• Consequence: TNKS NM_003747.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNKS	NM_003747.3	c.994+20514T>C		intron_variant	Intron 3 of 26	ENST00000310430.11	NP_003738.2
TNKS	XM_011543845.4	c.994+20514T>C		intron_variant	Intron 3 of 27		XP_011542147.1
TNKS	XM_011543846.4	c.994+20514T>C		intron_variant	Intron 3 of 26		XP_011542148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNKS	ENST00000310430.11	c.994+20514T>C		intron_variant	Intron 3 of 26	1	NM_003747.3	ENSP00000311579.6

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22742 AN: 152072 Hom.: 1889 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.156

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.150 AC: 22782 AN: 152188 Hom.: 1896 Cov.: 32 AF XY: 0.151 AC XY: 11207 AN XY: 74410

African (AFR) AF: 0.175 AC: 7250 AN: 41510

American (AMR) AF: 0.236 AC: 3608 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 349 AN: 3470

East Asian (EAS) AF: 0.227 AC: 1175 AN: 5180

South Asian (SAS) AF: 0.150 AC: 724 AN: 4826

European-Finnish (FIN) AF: 0.104 AC: 1101 AN: 10596

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8116 AN: 67988

Other (OTH) AF: 0.156 AC: 330 AN: 2112

Alfa AF: 0.108 Hom.: 543

Bravo AF: 0.164

Asia WGS AF: 0.177 AC: 617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.39
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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: rs11994018; hg19: chr8-9493701;