Genetic Variant TUBA3E:p.His309His (chr2-130193915-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_207312.3(TUBA3E):c.927T>C(p.His309His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 0 hom., cov: 33)

Exomes 𝑓: 0.012 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

TUBA3E
NM_207312.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.268

Variant links:

Genes affected

TUBA3E (HGNC:20765): (tubulin alpha 3e) Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulin. The genes encoding these microtubule constituents are part of the tubulin superfamily, which is composed of six distinct families. Genes from the alpha, beta and gamma tubulin families are found in all eukaryotes. The alpha and beta tubulins represent the major components of microtubules, while gamma tubulin plays a critical role in the nucleation of microtubule assembly. This gene encodes an alpha tubulin that highly conserved among species. A missense mutation in this gene has been potentially linked to microlissencephaly and global developmental delay. [provided by RefSeq, Jul 2016]

TUBA3E links:

MZT2B (HGNC:25886): (mitotic spindle organizing protein 2B) Located in cytosol; microtubule cytoskeleton; and nucleoplasm. Part of gamma-tubulin large complex. [provided by Alliance of Genome Resources, Apr 2022]

MZT2B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

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

BP6

Variant 2-130193915-A-G is Benign according to our data. Variant chr2-130193915-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 767821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.268 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBA3E	NM_207312.3 link	c.927T>C	p.His309His	synonymous_variant	Exon 4 of 5	ENST00000312988.9	NP_997195.2	Q6PEY2
MZT2B	XM_047445914.1 link	c.320-8410A>G		intron_variant	Intron 2 of 3		XP_047301870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBA3E	ENST00000312988.9 link	c.927T>C	p.His309His	synonymous_variant	Exon 4 of 5	1	NM_207312.3	ENSP00000318197.7		Q6PEY2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

5678

AN:

126024

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.00227

Gnomad AMR

AF:

0.0172

Gnomad ASJ

AF:

0.00894

Gnomad EAS

AF:

0.000969

Gnomad SAS

AF:

0.0144

Gnomad FIN

AF:

0.00965

Gnomad MID

AF:

0.0175

Gnomad NFE

AF:

0.0160

Gnomad OTH

AF:

0.0409

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0121

AC:

15148

AN:

1251560

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

7468

AN XY:

623832

show subpopulations

Gnomad4 AFR exome

AF:

0.182

Gnomad4 AMR exome

AF:

0.00936

Gnomad4 ASJ exome

AF:

0.00851

Gnomad4 EAS exome

AF:

0.000783

Gnomad4 SAS exome

AF:

0.0163

Gnomad4 FIN exome

AF:

0.0101

Gnomad4 NFE exome

AF:

0.00910

Gnomad4 OTH exome

AF:

0.0152

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0451

AC:

5690

AN:

126096

Hom.:

Cov.:

AF XY:

0.0437

AC XY:

2720

AN XY:

62188

show subpopulations

Gnomad4 AFR

AF:

0.161

Gnomad4 AMR

AF:

0.0173

Gnomad4 ASJ

AF:

0.00894

Gnomad4 EAS

AF:

0.000972

Gnomad4 SAS

AF:

0.0147

Gnomad4 FIN

AF:

0.00965

Gnomad4 NFE

AF:

0.0160

Gnomad4 OTH

AF:

0.0404

Alfa

AF:

0.0559

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Sep 28, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

3.9

DANN

Benign

0.77

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