Variant chr22-18126794-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018943.3(TUBA8):c.816C>T(p.Tyr272Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00282 in 1,614,040 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 39 hom., cov: 31)

Exomes 𝑓: 0.0016 ( 57 hom. )

Consequence

TUBA8
NM_018943.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.79

Variant links:

Genes affected

TUBA8 (HGNC:12410): (tubulin alpha 8) This gene encodes a member of the alpha tubulin protein family. Alpha tubulins are one of two core protein families (alpha and beta tubulins) that heterodimerize and assemble to form microtubules. Mutations in this gene are associated with polymicrogyria and optic nerve hypoplasia. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]

TUBA8 links:

ENSG00000288683 (HGNC:):

ENSG00000288683 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 22-18126794-C-T is Benign according to our data. Variant chr22-18126794-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 160174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-18126794-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.79 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBA8	NM_018943.3 linkuse as main transcript	c.816C>T	p.Tyr272Tyr	synonymous_variant	4/5	ENST00000330423.8	NP_061816.1	Q9NY65-1
TUBA8	NM_001193414.2 linkuse as main transcript	c.618C>T	p.Tyr206Tyr	synonymous_variant	4/5		NP_001180343.1	Q9NY65-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TUBA8	ENST00000330423.8 linkuse as main transcript	c.816C>T	p.Tyr272Tyr	synonymous_variant	4/5	1	NM_018943.3	ENSP00000333326.3	Q9NY65-1
ENSG00000288683	ENST00000474897.6 linkuse as main transcript	n.*706C>T		non_coding_transcript_exon_variant	8/9	5		ENSP00000434235.2	E9PRC5
ENSG00000288683	ENST00000474897.6 linkuse as main transcript	n.*706C>T		3_prime_UTR_variant	8/9	5		ENSP00000434235.2	E9PRC5

Frequencies

GnomAD3 genomes

AF:

0.0142

AC:

2160

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0490

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00563

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:

0.000382

Gnomad OTH

AF:

0.00961

GnomAD3 exomes

AF:

0.00391

AC:

984

AN:

251384

Hom.:

AF XY:

0.00290

AC XY:

394

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.0508

Gnomad AMR exome

AF:

0.00280

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00163

AC:

2384

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

1049

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0524

Gnomad4 AMR exome

AF:

0.00322

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000274

Gnomad4 OTH exome

AF:

0.00265

GnomAD4 genome

AF:

0.0142

AC:

2163

AN:

152190

Hom.:

Cov.:

AF XY:

0.0138

AC XY:

1025

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0489

Gnomad4 AMR

AF:

0.00562

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00951

Alfa

AF:

0.00653

Hom.:

Bravo

AF:

0.0162

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000415

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 06, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 14, 2013	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.2

DANN

Benign

0.82

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over