rs147339483

Variant names:

• chr6-3154697-G-A
• rs147339483
• NM_001069.3:c.504C>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001069.3(TUBB2A):​c.504C>T​(p.Ser168Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,612,650 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0055 (6 hom., cov: 30)
  • Exomes 𝑓: 0.00063 (11 hom.)
• Consequence: TUBB2A NM_001069.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.612

Genes affected

TUBB2A (HGNC:12412): (tubulin beta 2A class IIa) Microtubules, key participants in processes such as mitosis and intracellular transport, are composed of heterodimers of alpha- and beta-tubulins. The protein encoded by this gene is a beta-tubulin. Defects in this gene are associated with complex cortical dysplasia with other brain malformations-5. Two transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2015]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 6-3154697-G-A is Benign according to our data. Variant chr6-3154697-G-A is described in ClinVar as [Benign]. Clinvar id is 212496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-3154697-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.612 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0055 (834/151606) while in subpopulation AFR AF= 0.0187 (776/41434). AF 95% confidence interval is 0.0176. There are 6 homozygotes in gnomad4. There are 378 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 834 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBB2A	NM_001069.3	c.504C>T	p.Ser168Ser	synonymous_variant	Exon 4 of 4	ENST00000333628.4	NP_001060.1
TUBB2A	NM_001310315.2	c.249C>T	p.Ser83Ser	synonymous_variant	Exon 4 of 4		NP_001297244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBB2A	ENST00000333628.4	c.504C>T	p.Ser168Ser	synonymous_variant	Exon 4 of 4	1	NM_001069.3	ENSP00000369703.2

Frequencies

GnomAD3 genomes AF: 0.00552 AC: 836 AN: 151486 Hom.: 6 Cov.: 30

Gnomad AFR AF: 0.0188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0000738

Gnomad OTH AF: 0.00581

GnomAD3 exomes AF: 0.00148 AC: 372 AN: 250520 Hom.: 2 AF XY: 0.00105 AC XY: 142 AN XY: 135470

Gnomad AFR exome AF: 0.0195

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000797

Gnomad OTH exome AF: 0.000818

GnomAD4 exome AF: 0.000630 AC: 921 AN: 1461044 Hom.: 11 Cov.: 34 AF XY: 0.000577 AC XY: 419 AN XY: 726712

Gnomad4 AFR exome AF: 0.0221

Gnomad4 AMR exome AF: 0.00121

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000162

Gnomad4 OTH exome AF: 0.00146

GnomAD4 genome AF: 0.00550 AC: 834 AN: 151606 Hom.: 6 Cov.: 30 AF XY: 0.00510 AC XY: 378 AN XY: 74072

Gnomad4 AFR AF: 0.0187

Gnomad4 AMR AF: 0.00236

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000738

Gnomad4 OTH AF: 0.00575

Alfa AF: 0.00197 Hom.: 0

Bravo AF: 0.00645

EpiCase AF: 0.000109

EpiControl AF: 0.0000594

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Mar 22, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Aug 30, 2016

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	11
DANN	Benign	0.89

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: rs147339483; hg19: chr6-3154931;