chr8-9591841-A-G

Variant names:

• chr8-9591841-A-G
• rs6984737
• NM_003747.3:c.898+11458A>G

Variant summary

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

The NM_003747.3(TNKS):​c.898+11458A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.076 in 152,224 control chromosomes in the GnomAD database, including 483 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 0.076 (483 hom., cov: 32)
• Consequence: TNKS NM_003747.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.934
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNKS	NM_003747.3	c.898+11458A>G		intron_variant	Intron 2 of 26	ENST00000310430.11	NP_003738.2
TNKS	XM_011543845.4	c.898+11458A>G		intron_variant	Intron 2 of 27		XP_011542147.1
TNKS	XM_011543846.4	c.898+11458A>G		intron_variant	Intron 2 of 26		XP_011542148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNKS	ENST00000310430.11	c.898+11458A>G		intron_variant	Intron 2 of 26	1	NM_003747.3	ENSP00000311579.6
TNKS	ENST00000517770.2	c.898+11458A>G		intron_variant	Intron 2 of 27	4		ENSP00000428185.2
TNKS	ENST00000518281.5	c.187+11458A>G		intron_variant	Intron 2 of 26	2		ENSP00000429890.1
TNKS	ENST00000520408.5	c.898+11458A>G		intron_variant	Intron 2 of 10	2		ENSP00000428299.1

Frequencies

GnomAD3 genomes AF: 0.0760 AC: 11553 AN: 152104 Hom.: 479 Cov.: 32

Gnomad AFR AF: 0.0766

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0860

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.0966

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.0795

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0670

Gnomad OTH AF: 0.0666

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

GnomAD4 genome AF: 0.0760 AC: 11576 AN: 152224 Hom.: 483 Cov.: 32 AF XY: 0.0794 AC XY: 5903 AN XY: 74390

African (AFR) AF: 0.0767 AC: 3187 AN: 41550

American (AMR) AF: 0.0860 AC: 1315 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0516 AC: 179 AN: 3470

East Asian (EAS) AF: 0.0967 AC: 500 AN: 5172

South Asian (SAS) AF: 0.170 AC: 821 AN: 4816

European-Finnish (FIN) AF: 0.0795 AC: 842 AN: 10596

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0671 AC: 4561 AN: 68018

Other (OTH) AF: 0.0711 AC: 150 AN: 2110

Alfa AF: 0.0748 Hom.: 274

Bravo AF: 0.0736

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.30
DANN	Benign	0.60
PhyloP100		-0.93
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: rs6984737; hg19: chr8-9449351;