18-48404-T-G

Variant names:

• chr18-48404-T-G
• rs571677689
• NM_001358689.2:c.321A>C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001358689.2(TUBB8B):​c.321A>C​(p.Thr107Thr) 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 0.0028 (0 hom., cov: 35)
  • Exomes 𝑓: 0.000068 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TUBB8B NM_001358689.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.935

Genes affected

TUBB8B (HGNC:24983): (tubulin beta 8B) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 18-48404-T-G is Benign according to our data. Variant chr18-48404-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2672717.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.935 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBB8B	NM_001358689.2	c.321A>C	p.Thr107Thr	synonymous_variant	Exon 4 of 4	ENST00000308911.9	NP_001345618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBB8B	ENST00000308911.9	c.321A>C	p.Thr107Thr	synonymous_variant	Exon 4 of 4	6	NM_001358689.2	ENSP00000496713.1
TUBB8B	ENST00000594555.1	n.342A>C		non_coding_transcript_exon_variant	Exon 2 of 2	3
TUBB8B	ENST00000706408.1	n.1283A>C		non_coding_transcript_exon_variant	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 381 AN: 138654 Hom.: 0 Cov.: 35 FAILED QC

Gnomad AFR AF: 0.00895

Gnomad AMI AF: 0.00249

Gnomad AMR AF: 0.00161

Gnomad ASJ AF: 0.000919

Gnomad EAS AF: 0.000391

Gnomad SAS AF: 0.000445

Gnomad FIN AF: 0.00212

Gnomad MID AF: 0.00342

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.00207

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000676 AC: 97 AN: 1434234 Hom.: 0 Cov.: 37 AF XY: 0.0000631 AC XY: 45 AN XY: 713372

Gnomad4 AFR exome AF: 0.00123

Gnomad4 AMR exome AF: 0.0000689

Gnomad4 ASJ exome AF: 0.000322

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000355

Gnomad4 FIN exome AF: 0.0000577

Gnomad4 NFE exome AF: 0.0000356

Gnomad4 OTH exome AF: 0.0000684

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00276 AC: 383 AN: 138750 Hom.: 0 Cov.: 35 AF XY: 0.00304 AC XY: 206 AN XY: 67746

Gnomad4 AFR AF: 0.00898

Gnomad4 AMR AF: 0.00161

Gnomad4 ASJ AF: 0.000919

Gnomad4 EAS AF: 0.000392

Gnomad4 SAS AF: 0.000445

Gnomad4 FIN AF: 0.00212

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.00205

Alfa AF: 0.0117 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TUBB8B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.9
DANN	Benign	0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs571677689; hg19: chr18-48404;