Variant rs869025273 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PM5PP2PP5_Moderate

The NM_177987.3(TUBB8):c.5G>A(p.Arg2Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2M) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TUBB8
NM_177987.3 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 4.84

Variant links:

Genes affected

TUBB8 (HGNC:20773): (tubulin beta 8 class VIII) The protein encoded by this gene represents the primary beta-tubulin subunit of oocytes and the early embryo. Defects in this gene, which is primate-specific, are a cause of oocyte maturation defect 2 and infertility. [provided by RefSeq, Mar 2016]

TUBB8 links:

TUBB8 (HGNC:):

TUBB8 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr10-49234-C-A is described in Lovd as [Pathogenic].

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), TUBB8. . Trascript score misZ 3.4713 (greater than threshold 3.09). GenCC has associacion of gene with oocyte maturation defect 2.

PP5

Variant 10-49234-C-T is Pathogenic according to our data. Variant chr10-49234-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 221270.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-49234-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBB8	NM_177987.3 linkuse as main transcript	c.5G>A	p.Arg2Lys	missense_variant	1/4	ENST00000568584.6	NP_817124.1	Q3ZCM7
TUBB8	NM_001389618.1 linkuse as main transcript	c.-160+174G>A		intron_variant			NP_001376547.1
TUBB8	NM_001389619.1 linkuse as main transcript	c.-160+174G>A		intron_variant			NP_001376548.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBB8	ENST00000568584.6 linkuse as main transcript	c.5G>A	p.Arg2Lys	missense_variant	1/4	1	NM_177987.3	ENSP00000456206.2		Q3ZCM7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1432942

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710336

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Oocyte maturation defect 2

Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	OMIM	Apr 10, 2023	- -
Pathogenic, criteria provided, single submitter	literature only	SNPedia	Jan 21, 2016	Infertility, female -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.0049

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.017

.;T;.;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.52

T;T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.33

T;T;T;T

MetaSVM

Benign

-0.36

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.76

N;N;N;N

Sift

Pathogenic

0.0

.;.;D;.

Sift4G

Uncertain

0.053

T;T;D;D

Polyphen

0.24

.;B;.;.

Vest4

0.80

MutPred

0.47

Gain of ubiquitination at R2 (P = 0.0155);Gain of ubiquitination at R2 (P = 0.0155);Gain of ubiquitination at R2 (P = 0.0155);Gain of ubiquitination at R2 (P = 0.0155);

MVP

0.78

ClinPred

0.94

GERP RS

0.11

Varity_R

0.33

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.49

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.49

Position offset: -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