rs6994574

Positions:

• chr8-9720745-G-A
• chr8-9720745-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003747.3(TNKS):​c.1921+200G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 151,902 control chromosomes in the GnomAD database, including 27,131 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 0.59 (27131 hom., cov: 31)
• Consequence: TNKS NM_003747.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNKS	NM_003747.3	c.1921+200G>A		intron_variant		ENST00000310430.11
TNKS	XM_011543845.4	c.1921+200G>A		intron_variant
TNKS	XM_011543846.4	c.1921+200G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNKS	ENST00000310430.11	c.1921+200G>A		intron_variant		1	NM_003747.3	P1
TNKS	ENST00000519930.2	c.90+200G>A		intron_variant, NMD_transcript_variant		1
TNKS	ENST00000517770.2	c.1921+200G>A		intron_variant		4
TNKS	ENST00000518281.5	c.1210+200G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90298 AN: 151784 Hom.: 27122 Cov.: 31

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.637

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

GnomAD4 genome AF: 0.595 AC: 90340 AN: 151902 Hom.: 27131 Cov.: 31 AF XY: 0.590 AC XY: 43771 AN XY: 74232

Gnomad4 AFR AF: 0.556

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.760

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.563

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.633

Alfa AF: 0.627 Hom.: 13619

Bravo AF: 0.592

Asia WGS AF: 0.514 AC: 1787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.74
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs6994574; hg19: chr8-9578255;