rs77191445

Variant names:

• chr16-89933586-C-A
• NM_006086.4:c.277+8C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-89933586-C-A
• chr16-89933586-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006086.4(TUBB3):​c.277+8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TUBB3 NM_006086.4 splice_region, intron
• Scores: Splicing: ADA: 0.00005530
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.091368586).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBB3	NM_006086.4	c.277+8C>A		splice_region_variant, intron_variant	Intron 3 of 3	ENST00000315491.12	NP_006077.2
TUBB3	NM_001197181.2	c.61+8C>A		splice_region_variant, intron_variant	Intron 3 of 3		NP_001184110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBB3	ENST00000315491.12	c.277+8C>A		splice_region_variant, intron_variant	Intron 3 of 3	1	NM_006086.4	ENSP00000320295.7
ENSG00000198211	ENST00000556922.1	c.1318+8C>A		splice_region_variant, intron_variant	Intron 4 of 4	2		ENSP00000451560.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455074 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 724348

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.55
DANN	Benign	0.41
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.99	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.018
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.12	T
Vest4		0.072
MutPred		0.30		Loss of sheet (P = 0.0228);
MVP		0.50
ClinPred		0.052	T
GERP RS		-7.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000055
dbscSNV1_RF	Benign	0.0080
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-89999994;