8-9679917-A-G

Variant names:

• chr8-9679917-A-G
• rs6985140
• NM_003747.3:c.995-34A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003747.3(TNKS):​c.995-34A>G variant causes a intron change. The variant allele was found at a frequency of 0.0868 in 1,586,392 control chromosomes in the GnomAD database, including 6,874 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 0.097 (788 hom., cov: 32)
  • Exomes 𝑓: 0.086 (6086 hom.)
• Consequence: TNKS NM_003747.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.64
• Publications: 9 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNKS	NM_003747.3	c.995-34A>G		intron_variant	Intron 3 of 26	ENST00000310430.11	NP_003738.2
TNKS	XM_011543845.4	c.995-34A>G		intron_variant	Intron 3 of 27		XP_011542147.1
TNKS	XM_011543846.4	c.995-34A>G		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.995-34A>G		intron_variant	Intron 3 of 26	1	NM_003747.3	ENSP00000311579.6

Frequencies

GnomAD3 genomes AF: 0.0972 AC: 14785 AN: 152048 Hom.: 782 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0950

Gnomad ASJ AF: 0.0556

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.0963

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0803

Gnomad OTH AF: 0.0804

GnomAD2 exomes AF: 0.0995 AC: 24842 AN: 249628 AF XY: 0.104

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.0860

Gnomad ASJ exome AF: 0.0605

Gnomad EAS exome AF: 0.0952

Gnomad FIN exome AF: 0.0950

Gnomad NFE exome AF: 0.0817

Gnomad OTH exome AF: 0.0843

GnomAD4 exome AF: 0.0857 AC: 122904 AN: 1434226 Hom.: 6086 Cov.: 26 AF XY: 0.0888 AC XY: 63527 AN XY: 715064

African (AFR) AF: 0.122 AC: 4027 AN: 32902

American (AMR) AF: 0.0855 AC: 3816 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.0615 AC: 1597 AN: 25948

East Asian (EAS) AF: 0.0986 AC: 3899 AN: 39550

South Asian (SAS) AF: 0.184 AC: 15699 AN: 85490

European-Finnish (FIN) AF: 0.0954 AC: 5067 AN: 53128

Middle Eastern (MID) AF: 0.0704 AC: 403 AN: 5728

European-Non Finnish (NFE) AF: 0.0766 AC: 83304 AN: 1087488

Other (OTH) AF: 0.0858 AC: 5092 AN: 59374

GnomAD4 genome AF: 0.0974 AC: 14816 AN: 152166 Hom.: 788 Cov.: 32 AF XY: 0.100 AC XY: 7456 AN XY: 74382

African (AFR) AF: 0.123 AC: 5095 AN: 41494

American (AMR) AF: 0.0950 AC: 1452 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0556 AC: 193 AN: 3470

East Asian (EAS) AF: 0.102 AC: 526 AN: 5178

South Asian (SAS) AF: 0.180 AC: 868 AN: 4824

European-Finnish (FIN) AF: 0.0963 AC: 1020 AN: 10588

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0803 AC: 5459 AN: 68012

Other (OTH) AF: 0.0848 AC: 179 AN: 2112

Alfa AF: 0.0861 Hom.: 692

Bravo AF: 0.0961

Asia WGS AF: 0.168 AC: 584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Benign	0.82
PhyloP100		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs6985140; hg19: chr8-9537427; COSMIC: COSV60058316;