8-9711400-T-G

Variant names:

• chr8-9711400-T-G
• rs7825818
• NM_003747.3:c.1749+1180T>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.1749+1180T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.827 in 152,094 control chromosomes in the GnomAD database, including 52,198 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 0.83 (52198 hom., cov: 31)
• Consequence: TNKS NM_003747.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNKS	NM_003747.3	c.1749+1180T>G		intron_variant	Intron 11 of 26	ENST00000310430.11	NP_003738.2
TNKS	XM_011543845.4	c.1749+1180T>G		intron_variant	Intron 11 of 27		XP_011542147.1
TNKS	XM_011543846.4	c.1749+1180T>G		intron_variant	Intron 11 of 26		XP_011542148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNKS	ENST00000310430.11	c.1749+1180T>G		intron_variant	Intron 11 of 26	1	NM_003747.3	ENSP00000311579.6
TNKS	ENST00000517770.2	c.1749+1180T>G		intron_variant	Intron 11 of 27	4		ENSP00000428185.2
TNKS	ENST00000518281.5	c.1038+1180T>G		intron_variant	Intron 11 of 26	2		ENSP00000429890.1

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125708 AN: 151976 Hom.: 52154 Cov.: 31

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.859

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

GnomAD4 genome AF: 0.827 AC: 125803 AN: 152094 Hom.: 52198 Cov.: 31 AF XY: 0.825 AC XY: 61333 AN XY: 74336

African (AFR) AF: 0.829 AC: 34384 AN: 41494

American (AMR) AF: 0.888 AC: 13569 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3160 AN: 3472

East Asian (EAS) AF: 0.802 AC: 4142 AN: 5162

South Asian (SAS) AF: 0.883 AC: 4254 AN: 4820

European-Finnish (FIN) AF: 0.697 AC: 7358 AN: 10552

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.825 AC: 56115 AN: 67996

Other (OTH) AF: 0.860 AC: 1816 AN: 2112

Alfa AF: 0.809 Hom.: 5136

Bravo AF: 0.838

Asia WGS AF: 0.841 AC: 2926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.52
PhyloP100		-2.4
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: rs7825818; hg19: chr8-9568910;