rs531094726

chr15-42817047-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_173500.4(TTBK2):c.588C>T(p.Asn196=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,604,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: TTBK2 NM_173500.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.436

Genes affected

TTBK2 (HGNC:19141): (tau tubulin kinase 2) This gene encodes a serine-threonine kinase that putatively phosphorylates tau and tubulin proteins. Mutations in this gene cause spinocerebellar ataxia type 11 (SCA11); a neurodegenerative disease characterized by progressive ataxia and atrophy of the cerebellum and brainstem. [provided by RefSeq, Aug 2009]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 15-42817047-G-A is Benign according to our data. Variant chr15-42817047-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 448760.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.436 with no splicing effect.
• BS2: High AC in GnomAd at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTBK2	NM_173500.4	c.588C>T	p.Asn196=	synonymous_variant	7/15	ENST00000267890.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTBK2	ENST00000267890.11	c.588C>T	p.Asn196=	synonymous_variant	7/15	5	NM_173500.4	P1
TTBK2	ENST00000567840.5	c.588C>T	p.Asn196=	synonymous_variant	7/12	1
TTBK2	ENST00000567274.5	c.483C>T	p.Asn161=	synonymous_variant	6/11	5

Frequencies

GnomAD3 genomes AF: 0.0000527 AC: 8 AN: 151868 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000160 AC: 4 AN: 249386 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135326

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000124 AC: 18 AN: 1453094 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10 AN XY: 723090

Gnomad4 AFR exome AF: 0.0000602

Gnomad4 AMR exome AF: 0.0000450

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000994

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome AF: 0.0000527 AC: 8 AN: 151868 Hom.: 0 Cov.: 30 AF XY: 0.0000539 AC XY: 4 AN XY: 74182

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000772 Hom.: 0

Bravo AF: 0.0000642

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jun 21, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	8.4
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs531094726; hg19: chr15-43109245; COSMIC: COSV51158327;