10-47792-A-G

Position:

• chr10-47792-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_177987.3(TUBB8):​c.600T>C​(p.Phe200Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,596,546 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0082 (7 hom., cov: 36)
  • Exomes 𝑓: 0.00060 (4 hom.)
• Consequence: TUBB8 NM_177987.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=1.39 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00824 (1181/143252) while in subpopulation AFR AF= 0.0294 (1107/37702). AF 95% confidence interval is 0.0279. There are 7 homozygotes in gnomad4. There are 560 alleles in male gnomad4 subpopulation. Median coverage is 36. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBB8	NM_177987.3	c.600T>C	p.Phe200Phe	synonymous_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.600T>C	p.Phe200Phe	synonymous_variant	4/4	1	NM_177987.3	ENSP00000456206.2

Frequencies

GnomAD3 genomes AF: 0.00825 AC: 1181 AN: 143132 Hom.: 7 Cov.: 36

Gnomad AFR AF: 0.0295

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00293

Gnomad ASJ AF: 0.000305

Gnomad EAS AF: 0.000600

Gnomad SAS AF: 0.000218

Gnomad FIN AF: 0.000595

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000920

Gnomad OTH AF: 0.00777

GnomAD3 exomes AF: 0.00156 AC: 390 AN: 249742 Hom.: 5 AF XY: 0.00121 AC XY: 164 AN XY: 135300

Gnomad AFR exome AF: 0.0228

Gnomad AMR exome AF: 0.000726

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.000657

GnomAD4 exome AF: 0.000599 AC: 870 AN: 1453294 Hom.: 4 Cov.: 78 AF XY: 0.000517 AC XY: 374 AN XY: 723040

Gnomad4 AFR exome AF: 0.0221

Gnomad4 AMR exome AF: 0.00105

Gnomad4 ASJ exome AF: 0.0000386

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000350

Gnomad4 FIN exome AF: 0.0000767

Gnomad4 NFE exome AF: 0.0000172

Gnomad4 OTH exome AF: 0.000967

GnomAD4 genome AF: 0.00824 AC: 1181 AN: 143252 Hom.: 7 Cov.: 36 AF XY: 0.00801 AC XY: 560 AN XY: 69886

Gnomad4 AFR AF: 0.0294

Gnomad4 AMR AF: 0.00293

Gnomad4 ASJ AF: 0.000305

Gnomad4 EAS AF: 0.000601

Gnomad4 SAS AF: 0.000218

Gnomad4 FIN AF: 0.000595

Gnomad4 NFE AF: 0.0000921

Gnomad4 OTH AF: 0.00768

Alfa AF: 0.00341 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.1
DANN	Benign	0.29

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: rs148025238; hg19: chr10-93732; COSMIC: COSV59116339; COSMIC: COSV59116339;