rs78656983

Variant names:

• chr16-89932550-C-A
• rs78656983
• NM_006086.4:c.58-21C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-89932550-C-A
• chr16-89932550-C-G
• chr16-89932550-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_006086.4(TUBB3):​c.58-21C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,608,066 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (3 hom.)
• Consequence: TUBB3 NM_006086.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

Genes affected

TUBB3 (HGNC:20772): (tubulin beta 3 class III) This gene encodes a class III member of the beta tubulin protein family. Beta tubulins are one of two core protein families (alpha and beta tubulins) that heterodimerize and assemble to form microtubules. This protein is primarily expressed in neurons and may be involved in neurogenesis and axon guidance and maintenance. Mutations in this gene are the cause of congenital fibrosis of the extraocular muscles type 3. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 6. [provided by RefSeq, Oct 2010]

ENSG00000198211 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 16-89932550-C-A is Benign according to our data. Variant chr16-89932550-C-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00145 (221/152334) while in subpopulation NFE AF= 0.0022 (150/68046). AF 95% confidence interval is 0.00192. There are 0 homozygotes in gnomad4. There are 96 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBB3	NM_006086.4	c.58-21C>A		intron_variant	Intron 1 of 3	ENST00000315491.12	NP_006077.2
TUBB3	NM_001197181.2	c.-159-21C>A		intron_variant	Intron 1 of 3		NP_001184110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBB3	ENST00000315491.12	c.58-21C>A		intron_variant	Intron 1 of 3	1	NM_006086.4	ENSP00000320295.7
ENSG00000198211	ENST00000556922.1	c.1099-21C>A		intron_variant	Intron 2 of 4	2		ENSP00000451560.1

Frequencies

GnomAD3 genomes AF: 0.00145 AC: 221 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00220

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00121 AC: 304 AN: 250308 Hom.: 0 AF XY: 0.00131 AC XY: 177 AN XY: 135588

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.000723

Gnomad ASJ exome AF: 0.00309

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000720

Gnomad FIN exome AF: 0.000971

Gnomad NFE exome AF: 0.00170

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00167 AC: 2432 AN: 1455732 Hom.: 3 Cov.: 30 AF XY: 0.00168 AC XY: 1214 AN XY: 724596

Gnomad4 AFR exome AF: 0.000300

Gnomad4 AMR exome AF: 0.00123

Gnomad4 ASJ exome AF: 0.00268

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000847

Gnomad4 FIN exome AF: 0.000979

Gnomad4 NFE exome AF: 0.00187

Gnomad4 OTH exome AF: 0.00160

GnomAD4 genome AF: 0.00145 AC: 221 AN: 152334 Hom.: 0 Cov.: 33 AF XY: 0.00129 AC XY: 96 AN XY: 74482

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.00189

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00220

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000766 Hom.: 2

Bravo AF: 0.00164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.4
DANN	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs78656983; hg19: chr16-89998958;