rs361557

chr22-18128456-A-Gchr22-18128456-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018943.3(TUBA8):c.1056+1422A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 152,090 control chromosomes in the GnomAD database, including 17,433 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (17433 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TUBA8 NM_018943.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.515

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBA8	NM_018943.3	c.1056+1422A>G		intron_variant		ENST00000330423.8
TUBA8	NM_001193414.2	c.858+1422A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBA8	ENST00000330423.8	c.1056+1422A>G		intron_variant		1	NM_018943.3	P1
	ENST00000623543.1	n.2699T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.395 AC: 60087 AN: 151972 Hom.: 17377 Cov.: 32

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.349

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 20 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 14

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.396 AC: 60205 AN: 152090 Hom.: 17433 Cov.: 32 AF XY: 0.396 AC XY: 29438 AN XY: 74356

Gnomad4 AFR AF: 0.792

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.353

Alfa AF: 0.236 Hom.: 9252

Bravo AF: 0.430

Asia WGS AF: 0.549 AC: 1905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.59
Dann	Benign	0.37

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: rs361557; hg19: chr22-18611223; COSMIC: COSV57813534; COSMIC: COSV57813534;