22-18126794-C-T

Variant names:

• chr22-18126794-C-T
• rs2234332
• NM_018943.3:c.816C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018943.3(TUBA8):​c.816C>T​(p.Tyr272Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00282 in 1,614,040 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (39 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (57 hom.)
• Consequence: TUBA8 NM_018943.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.79
• Publications: 3 publications found

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]

TUBA8 Gene-Disease associations (from GenCC):

• polymicrogyria with optic nerve hypoplasia

  Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, ClinGen

ENSG00000288683 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 22-18126794-C-T is Benign according to our data. Variant chr22-18126794-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 160174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.79 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0503 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018943.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBA8	NM_018943.3	MANE Select	c.816C>T	p.Tyr272Tyr	synonymous	Exon 4 of 5	NP_061816.1	Q9NY65-1
	TUBA8	NM_001193414.2		c.618C>T	p.Tyr206Tyr	synonymous	Exon 4 of 5	NP_001180343.1	Q9NY65-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBA8	ENST00000330423.8	TSL:1 MANE Select	c.816C>T	p.Tyr272Tyr	synonymous	Exon 4 of 5	ENSP00000333326.3	Q9NY65-1
	TUBA8	ENST00000416740.2	TSL:1	c.618C>T	p.Tyr206Tyr	synonymous	Exon 4 of 5	ENSP00000412646.2	Q9NY65-2
	ENSG00000288683	ENST00000474897.6	TSL:5	n.*706C>T		non_coding_transcript_exon	Exon 8 of 9	ENSP00000434235.2	E9PRC5

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 2160 AN: 152072 Hom.: 39 Cov.: 31

Gnomad AFR AF: 0.0490

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00563

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: 0.000382

Gnomad OTH AF: 0.00961

GnomAD2 exomes AF: 0.00391 AC: 984 AN: 251384 AF XY: 0.00290

Gnomad AFR exome AF: 0.0508

Gnomad AMR exome AF: 0.00280

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000352

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00163 AC: 2384 AN: 1461850 Hom.: 57 Cov.: 31 AF XY: 0.00144 AC XY: 1049 AN XY: 727224

African (AFR) AF: 0.0524 AC: 1754 AN: 33480

American (AMR) AF: 0.00322 AC: 144 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5768

European-Non Finnish (NFE) AF: 0.000274 AC: 305 AN: 1111984

Other (OTH) AF: 0.00265 AC: 160 AN: 60394

GnomAD4 genome AF: 0.0142 AC: 2163 AN: 152190 Hom.: 39 Cov.: 31 AF XY: 0.0138 AC XY: 1025 AN XY: 74414

African (AFR) AF: 0.0489 AC: 2031 AN: 41498

American (AMR) AF: 0.00562 AC: 86 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68020

Other (OTH) AF: 0.00951 AC: 20 AN: 2104

Alfa AF: 0.0112 Hom.: 35

Bravo AF: 0.0162

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.2
DANN	Benign	0.82
PhyloP100		-1.8
PromoterAI		-0.030	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs2234332; hg19: chr22-18609561; COSMIC: COSV57813724; COSMIC: COSV57813724;