chr6-43254624-C-T

Variant names:

• chr6-43254624-C-T
• rs7743427
• NM_032538.3:c.549C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_032538.3(TTBK1):​c.549C>T​(p.Tyr183Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00297 in 1,589,912 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (66 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (51 hom.)
• Consequence: TTBK1 NM_032538.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.40
• Publications: 2 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 6-43254624-C-T is Benign according to our data. Variant chr6-43254624-C-T is described in ClinVar as Benign. ClinVar VariationId is 783462.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.4 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0507 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.549C>T	p.Tyr183Tyr	synonymous	Exon 6 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.549C>T	p.Tyr183Tyr	synonymous	Exon 6 of 15	ENSP00000259750.4	Q5TCY1-1
	TTBK1	ENST00000703836.1		c.549C>T	p.Tyr183Tyr	synonymous	Exon 5 of 13	ENSP00000515493.1	A0A994J709
	TTBK1	ENST00000304139.6	TSL:5	n.558C>T		non_coding_transcript_exon	Exon 5 of 13

Frequencies

GnomAD3 genomes AF: 0.0151 AC: 2305 AN: 152244 Hom.: 66 Cov.: 32

Gnomad AFR AF: 0.0526

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00438

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00814

GnomAD2 exomes AF: 0.00413 AC: 939 AN: 227360 AF XY: 0.00279

Gnomad AFR exome AF: 0.0523

Gnomad AMR exome AF: 0.00220

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000534

Gnomad NFE exome AF: 0.000221

Gnomad OTH exome AF: 0.00200

GnomAD4 exome AF: 0.00168 AC: 2409 AN: 1437550 Hom.: 51 Cov.: 31 AF XY: 0.00141 AC XY: 1005 AN XY: 714124

African (AFR) AF: 0.0562 AC: 1829 AN: 32556

American (AMR) AF: 0.00276 AC: 110 AN: 39848

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24626

East Asian (EAS) AF: 0.00 AC: 0 AN: 38862

South Asian (SAS) AF: 0.0000973 AC: 8 AN: 82228

European-Finnish (FIN) AF: 0.000398 AC: 21 AN: 52746

Middle Eastern (MID) AF: 0.00406 AC: 23 AN: 5670

European-Non Finnish (NFE) AF: 0.000211 AC: 232 AN: 1101622

Other (OTH) AF: 0.00313 AC: 186 AN: 59392

GnomAD4 genome AF: 0.0151 AC: 2307 AN: 152362 Hom.: 66 Cov.: 32 AF XY: 0.0144 AC XY: 1076 AN XY: 74500

African (AFR) AF: 0.0526 AC: 2186 AN: 41590

American (AMR) AF: 0.00438 AC: 67 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10620

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68034

Other (OTH) AF: 0.00806 AC: 17 AN: 2110

Alfa AF: 0.00544 Hom.: 41

Bravo AF: 0.0172

Asia WGS AF: 0.00318 AC: 11 AN: 3478

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
BayesDel_noAF	Benign	-0.43
CADD	Benign	8.4
DANN	Benign	0.62
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7743427; hg19: chr6-43222362;