22-18121367-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_018943.3(TUBA8):c.4-112C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 928,756 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (17 hom., cov: 32)
  • Exomes 𝑓: 0.013 (89 hom.)
• Consequence: TUBA8 NM_018943.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0230

Genes affected

TUBA8 (HGNC:12410): (tubulin alpha 8) This gene encodes a member of the alpha tubulin protein family. Alpha tubulins are one of two core protein families (alpha and beta tubulins) that heterodimerize and assemble to form microtubules. Mutations in this gene are associated with polymicrogyria and optic nerve hypoplasia. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 22-18121367-C-T is Benign according to our data. Variant chr22-18121367-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1205249.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0111 (1695/152320) while in subpopulation NFE AF= 0.018 (1227/68020). AF 95% confidence interval is 0.0172. There are 17 homozygotes in gnomad4. There are 821 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 17 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBA8	NM_018943.3	c.4-112C>T		intron_variant		ENST00000330423.8
TUBA8	NM_001193414.2	c.-195-112C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBA8	ENST00000330423.8	c.4-112C>T		intron_variant		1	NM_018943.3	P1
	ENST00000623543.1	n.9788G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1695 AN: 152202 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.00383

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00582

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0180

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0180

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.0105 AC: 2123 AN: 202232 Hom.: 13 AF XY: 0.0106 AC XY: 1172 AN XY: 110142

Gnomad AFR exome AF: 0.00319

Gnomad AMR exome AF: 0.00342

Gnomad ASJ exome AF: 0.00233

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00243

Gnomad FIN exome AF: 0.0191

Gnomad NFE exome AF: 0.0170

Gnomad OTH exome AF: 0.00978

GnomAD4 exome AF: 0.0135 AC: 10462 AN: 776436 Hom.: 89 Cov.: 10 AF XY: 0.0129 AC XY: 5235 AN XY: 407368

Gnomad4 AFR exome AF: 0.00269

Gnomad4 AMR exome AF: 0.00367

Gnomad4 ASJ exome AF: 0.00163

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00249

Gnomad4 FIN exome AF: 0.0196

Gnomad4 NFE exome AF: 0.0172

Gnomad4 OTH exome AF: 0.0125

GnomAD4 genome AF: 0.0111 AC: 1695 AN: 152320 Hom.: 17 Cov.: 32 AF XY: 0.0110 AC XY: 821 AN XY: 74480

Gnomad4 AFR AF: 0.00382

Gnomad4 AMR AF: 0.00582

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0180

Gnomad4 NFE AF: 0.0180

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.0131 Hom.: 2

Bravo AF: 0.00980

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.5
Dann	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.61		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.61		Position offset: -2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2234323; hg19: chr22-18604134;