NM_006082.3:c.492G>A

Variant names:

• chr12-49128822-C-T
• rs1057548
• NM_006082.3:c.492G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_006082.3(TUBA1B):​c.492G>A​(p.Lys164Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,589,318 control chromosomes in the GnomAD database, including 78,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10048 hom., cov: 30)
  • Exomes 𝑓: 0.34 (68764 hom.)
• Consequence: TUBA1B NM_006082.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.61
• Publications: 20 publications found

Genes affected

TUBA1B (HGNC:18809): (tubulin alpha 1b) Enables double-stranded RNA binding activity and ubiquitin protein ligase binding activity. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Predicted to act upstream of or within cellular response to interleukin-4. Located in microtubule. [provided by Alliance of Genome Resources, Apr 2022]

TUBA1B-AS1 (HGNC:56356): (TUBA1B antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 12-49128822-C-T is Benign according to our data. Variant chr12-49128822-C-T is described in ClinVar as Benign. ClinVar VariationId is 1236526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.61 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006082.3. 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
	TUBA1B	NM_006082.3	MANE Select	c.492G>A	p.Lys164Lys	synonymous	Exon 4 of 4	NP_006073.2	P68363-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBA1B	ENST00000336023.9	TSL:1 MANE Select	c.492G>A	p.Lys164Lys	synonymous	Exon 4 of 4	ENSP00000336799.5	P68363-1
	TUBA1B	ENST00000332858.10	TSL:1	n.2162G>A		non_coding_transcript_exon	Exon 3 of 3
	TUBA1B	ENST00000920098.1		c.435G>A	p.Lys145Lys	synonymous	Exon 4 of 4	ENSP00000590157.1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53780 AN: 151292 Hom.: 10049 Cov.: 30

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.341

GnomAD2 exomes AF: 0.356 AC: 85811 AN: 240850 AF XY: 0.361

Gnomad AFR exome AF: 0.315

Gnomad AMR exome AF: 0.314

Gnomad ASJ exome AF: 0.241

Gnomad EAS exome AF: 0.685

Gnomad FIN exome AF: 0.360

Gnomad NFE exome AF: 0.302

Gnomad OTH exome AF: 0.337

GnomAD4 exome AF: 0.336 AC: 482453 AN: 1437908 Hom.: 68764 Cov.: 88 AF XY: 0.340 AC XY: 243308 AN XY: 715188

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.317 AC: 10481 AN: 33040

American (AMR) AF: 0.321 AC: 14044 AN: 43816

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 6681 AN: 25746

East Asian (EAS) AF: 0.691 AC: 26978 AN: 39064

South Asian (SAS) AF: 0.490 AC: 41024 AN: 83668

European-Finnish (FIN) AF: 0.375 AC: 19866 AN: 52994

Middle Eastern (MID) AF: 0.247 AC: 1411 AN: 5720

European-Non Finnish (NFE) AF: 0.312 AC: 341635 AN: 1094346

Other (OTH) AF: 0.342 AC: 20333 AN: 59514

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.355 AC: 53796 AN: 151410 Hom.: 10048 Cov.: 30 AF XY: 0.362 AC XY: 26787 AN XY: 73924

African (AFR) AF: 0.342 AC: 14082 AN: 41192

American (AMR) AF: 0.328 AC: 4984 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 918 AN: 3468

East Asian (EAS) AF: 0.713 AC: 3659 AN: 5134

South Asian (SAS) AF: 0.547 AC: 2616 AN: 4784

European-Finnish (FIN) AF: 0.381 AC: 3995 AN: 10482

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22570 AN: 67858

Other (OTH) AF: 0.339 AC: 712 AN: 2102

Alfa AF: 0.323 Hom.: 2094

Bravo AF: 0.348

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	7.7
DANN	Benign	0.90
PhyloP100		2.6
Mutation Taster		=84/16	polymorphism (auto)

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: rs1057548; hg19: chr12-49522605; COSMIC: COSV60136316; COSMIC: COSV60136316;