rs3800294

Variant names:

• chr6-43263232-G-C
• rs3800294
• NM_032538.3:c.1868G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-43263232-G-C
• chr6-43263232-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032538.3(TTBK1):​c.1868G>C​(p.Gly623Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,569,006 control chromosomes in the GnomAD database, including 91,154 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (9030 hom., cov: 33)
  • Exomes 𝑓: 0.34 (82124 hom.)
• Consequence: TTBK1 NM_032538.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.86
• Publications: 25 publications found

Genes affected

TTBK1 (HGNC:19140): (tau tubulin kinase 1) Summary:This gene belongs to the casein kinase 1 superfamily. The encoded protein is a neuron-specific, serine/threonine and tyrosine kinase, which regulates phosphorylation of tau, a protein that associates with microtubule assemblies and stabilizes them. Genetic variants in this gene are associated with Alzheimer's disease. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034447312).
• BP6: Variant 6-43263232-G-C is Benign according to our data. Variant chr6-43263232-G-C is described in ClinVar as Benign. ClinVar VariationId is 1341645.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032538.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTBK1	NM_032538.3	MANE Select	c.1868G>C	p.Gly623Ala	missense	Exon 13 of 15	NP_115927.1	Q5TCY1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTBK1	ENST00000259750.9	TSL:1 MANE Select	c.1868G>C	p.Gly623Ala	missense	Exon 13 of 15	ENSP00000259750.4	Q5TCY1-1
	TTBK1	ENST00000703836.1		c.1868G>C	p.Gly623Ala	missense	Exon 12 of 13	ENSP00000515493.1	A0A994J709
	TTBK1	ENST00000304139.6	TSL:5	n.1877G>C		non_coding_transcript_exon	Exon 12 of 13

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52291 AN: 152014 Hom.: 9024 Cov.: 33

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.340

GnomAD2 exomes AF: 0.320 AC: 57073 AN: 178416 AF XY: 0.322

Gnomad AFR exome AF: 0.344

Gnomad AMR exome AF: 0.268

Gnomad ASJ exome AF: 0.290

Gnomad EAS exome AF: 0.335

Gnomad FIN exome AF: 0.357

Gnomad NFE exome AF: 0.327

Gnomad OTH exome AF: 0.312

GnomAD4 exome AF: 0.340 AC: 481633 AN: 1416874 Hom.: 82124 Cov.: 48 AF XY: 0.340 AC XY: 238006 AN XY: 700430

African (AFR) AF: 0.348 AC: 11354 AN: 32650

American (AMR) AF: 0.269 AC: 10424 AN: 38732

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 7486 AN: 25020

East Asian (EAS) AF: 0.344 AC: 13009 AN: 37806

South Asian (SAS) AF: 0.328 AC: 26460 AN: 80642

European-Finnish (FIN) AF: 0.360 AC: 17720 AN: 49226

Middle Eastern (MID) AF: 0.281 AC: 1578 AN: 5620

European-Non Finnish (NFE) AF: 0.343 AC: 373864 AN: 1088692

Other (OTH) AF: 0.337 AC: 19738 AN: 58486

GnomAD4 genome AF: 0.344 AC: 52316 AN: 152132 Hom.: 9030 Cov.: 33 AF XY: 0.343 AC XY: 25536 AN XY: 74380

African (AFR) AF: 0.352 AC: 14619 AN: 41512

American (AMR) AF: 0.329 AC: 5028 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1065 AN: 3470

East Asian (EAS) AF: 0.361 AC: 1860 AN: 5156

South Asian (SAS) AF: 0.323 AC: 1558 AN: 4822

European-Finnish (FIN) AF: 0.362 AC: 3833 AN: 10598

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.343 AC: 23327 AN: 67964

Other (OTH) AF: 0.338 AC: 714 AN: 2114

Alfa AF: 0.287 Hom.: 1796

Bravo AF: 0.339

TwinsUK AF: 0.334 AC: 1239

ALSPAC AF: 0.343 AC: 1322

ESP6500AA AF: 0.312 AC: 1348

ESP6500EA AF: 0.317 AC: 2693

ExAC AF: 0.271 AC: 31196

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	14
DANN	Benign	0.66
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.099	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.9
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.11
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.016
MPC		0.34
ClinPred		0.00058	T
GERP RS		3.8
Varity_R		0.050
gMVP		0.18
Mutation Taster		=99/1	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: rs3800294; hg19: chr6-43230970; COSMIC: COSV52487992;