10-47353-T-C

Position:

• chr10-47353-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_177987.3(TUBB8):​c.1039A>G​(p.Asn347Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 27)
  • Failed GnomAD Quality Control
• Consequence: TUBB8 NM_177987.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.02

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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). The gene has 36 curated pathogenic missense variants (we use a threshold of 10). The gene has 9 curated benign missense variants. GenCC has associacion of the gene with oocyte maturation defect 2.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBB8	NM_177987.3	c.1039A>G	p.Asn347Asp	missense_variant	4/4	ENST00000568584.6	NP_817124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBB8	ENST00000568584.6	c.1039A>G	p.Asn347Asp	missense_variant	4/4	1	NM_177987.3	ENSP00000456206.2
TUBB8	ENST00000564130.2	c.937A>G	p.Asn313Asp	missense_variant	4/4	5		ENSP00000457610.1
TUBB8	ENST00000568866.5	c.928A>G	p.Asn310Asp	missense_variant	3/3	5		ENSP00000457062.1
TUBB8	ENST00000561967	c.*702A>G		3_prime_UTR_variant	4/4	5		ENSP00000454878.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152102 Hom.: 0 Cov.: 27 FAILED QC

Gnomad AFR AF: 0.00

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

GnomAD4 exome Cov.: 31

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 152216 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 74444

Gnomad4 AFR AF: 0.00

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Benign	0.69
DEOGEN2	Uncertain	0.51	.;.;D
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.54	D;D;D
MetaSVM	Benign	-0.40	T
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.9	D;D;D
Sift	Benign	0.039	D;.;.
Sift4G	Uncertain	0.041	D;D;T
Polyphen		0.016	.;.;B
Vest4		0.43
MutPred		0.60		.;.;Loss of ubiquitination at K350 (P = 0.0653);
MVP		0.86
ClinPred		0.36	T
Varity_R		0.75
gMVP		0.73

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

Other links and lift over

dbSNP: rs4881159; hg19: chr10-93293;