22-18110916-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_018943.3(TUBA8):c.3+48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00244 in 1,539,210 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0088 (16 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (17 hom.)
• Consequence: TUBA8 NM_018943.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.346

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 22-18110916-G-A is Benign according to our data. Variant chr22-18110916-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1198662.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00883 (1345/152286) while in subpopulation AFR AF= 0.0253 (1052/41572). AF 95% confidence interval is 0.024. There are 16 homozygotes in gnomad4. There are 617 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 15 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBA8	NM_018943.3	c.3+48G>A		intron_variant		ENST00000330423.8
TUBA8	NM_001193414.2	c.-196+77G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBA8	ENST00000330423.8	c.3+48G>A		intron_variant		1	NM_018943.3	P1
	ENST00000623543.1	n.20239C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00878 AC: 1336 AN: 152170 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.0252

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00116

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.00348 AC: 486 AN: 139732 Hom.: 5 AF XY: 0.00276 AC XY: 209 AN XY: 75776

Gnomad AFR exome AF: 0.0263

Gnomad AMR exome AF: 0.00626

Gnomad ASJ exome AF: 0.00595

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000869

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000936

Gnomad OTH exome AF: 0.00615

GnomAD4 exome AF: 0.00174 AC: 2414 AN: 1386924 Hom.: 17 Cov.: 30 AF XY: 0.00159 AC XY: 1088 AN XY: 684880

Gnomad4 AFR exome AF: 0.0260

Gnomad4 AMR exome AF: 0.00674

Gnomad4 ASJ exome AF: 0.00652

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.0000288

Gnomad4 NFE exome AF: 0.000816

Gnomad4 OTH exome AF: 0.00435

GnomAD4 genome AF: 0.00883 AC: 1345 AN: 152286 Hom.: 16 Cov.: 32 AF XY: 0.00829 AC XY: 617 AN XY: 74464

Gnomad4 AFR AF: 0.0253

Gnomad4 AMR AF: 0.0103

Gnomad4 ASJ AF: 0.00662

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00116

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.00215 Hom.: 2

Bravo AF: 0.0111

Asia WGS AF: 0.00115 AC: 4 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

Feb 06, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	1.7
Dann	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs58296327; hg19: chr22-18593682;