22-18110514-G-A

Position:

• chr22-18110514-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000474897.6(ENSG00000288683):​n.815-10965G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00731 in 422,164 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (72 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (11 hom.)
• Consequence: ENSG00000288683 ENST00000474897.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.691

Genes affected

ENSG00000288683 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 22-18110514-G-A is Benign according to our data. Variant chr22-18110514-G-A is described in ClinVar as [Benign]. Clinvar id is 1246318.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000288683	ENST00000474897.6	n.815-10965G>A		intron_variant		5		ENSP00000434235.2
TUBA8	ENST00000680175.1	c.-352G>A		5_prime_UTR_variant	1/6			ENSP00000505461.1
TUBA8	ENST00000679963.1	c.-258G>A		5_prime_UTR_variant	1/5			ENSP00000505896.1
TUBA8	ENST00000426208.5	c.-258G>A		5_prime_UTR_variant	1/3	3		ENSP00000407624.1

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2558 AN: 152222 Hom.: 72 Cov.: 32

Gnomad AFR AF: 0.0581

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00680

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0101

GnomAD4 exome AF: 0.00192 AC: 518 AN: 269824 Hom.: 11 Cov.: 0 AF XY: 0.00180 AC XY: 254 AN XY: 141436

Gnomad4 AFR exome AF: 0.0569

Gnomad4 AMR exome AF: 0.00523

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000374

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000429

Gnomad4 OTH exome AF: 0.00470

GnomAD4 genome AF: 0.0169 AC: 2568 AN: 152340 Hom.: 72 Cov.: 32 AF XY: 0.0161 AC XY: 1199 AN XY: 74488

Gnomad4 AFR AF: 0.0582

Gnomad4 AMR AF: 0.00679

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.00995

Alfa AF: 0.00935 Hom.: 5

Bravo AF: 0.0187

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.9
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2234321; hg19: chr22-18593280;