NM_003747.3:c.994+4178A>G

Variant names:

• chr8-9619855-A-G
• rs4474027
• NM_003747.3:c.994+4178A>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.994+4178A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0855 in 149,986 control chromosomes in the GnomAD database, including 572 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 0.085 (572 hom., cov: 29)
• Consequence: TNKS NM_003747.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• 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 (SAS) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNKS	NM_003747.3	c.994+4178A>G		intron_variant	Intron 3 of 26	ENST00000310430.11	NP_003738.2
TNKS	XM_011543845.4	c.994+4178A>G		intron_variant	Intron 3 of 27		XP_011542147.1
TNKS	XM_011543846.4	c.994+4178A>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.994+4178A>G		intron_variant	Intron 3 of 26	1	NM_003747.3	ENSP00000311579.6

Frequencies

GnomAD3 genomes AF: 0.0854 AC: 12795 AN: 149884 Hom.: 569 Cov.: 29

Gnomad AFR AF: 0.0966

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0935

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.0968

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.0806

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0729

Gnomad OTH AF: 0.0789

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

GnomAD4 genome AF: 0.0855 AC: 12817 AN: 149986 Hom.: 572 Cov.: 29 AF XY: 0.0882 AC XY: 6434 AN XY: 72976

African (AFR) AF: 0.0967 AC: 3928 AN: 40638

American (AMR) AF: 0.0935 AC: 1407 AN: 15050

Ashkenazi Jewish (ASJ) AF: 0.0671 AC: 233 AN: 3470

East Asian (EAS) AF: 0.0969 AC: 493 AN: 5090

South Asian (SAS) AF: 0.171 AC: 809 AN: 4718

European-Finnish (FIN) AF: 0.0806 AC: 805 AN: 9982

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.0729 AC: 4941 AN: 67748

Other (OTH) AF: 0.0833 AC: 174 AN: 2088

Alfa AF: 0.0623 Hom.: 154

Bravo AF: 0.0850

Asia WGS AF: 0.162 AC: 562 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	2.3
DANN	Benign	0.64
PhyloP100		-0.043
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: rs4474027; hg19: chr8-9477365;