chr12-49128795-T-C

Variant names:

• chr12-49128795-T-C
• rs1057725
• NM_006082.3:c.519A>G

Variant summary

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

The NM_006082.3(TUBA1B):​c.519A>G​(p.Pro173Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 1,487,486 control chromosomes in the GnomAD database, including 123,890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (16481 hom., cov: 28)
  • Exomes 𝑓: 0.36 (107409 hom.)
• Consequence: TUBA1B NM_006082.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.21
• Publications: 11 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 12-49128795-T-C is Benign according to our data. Variant chr12-49128795-T-C is described in ClinVar as Benign. ClinVar VariationId is 768541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.694 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.519A>G	p.Pro173Pro	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.519A>G	p.Pro173Pro	synonymous	Exon 4 of 4	ENSP00000336799.5	P68363-1
	TUBA1B	ENST00000332858.10	TSL:1	n.2189A>G		non_coding_transcript_exon	Exon 3 of 3
	TUBA1B	ENST00000920098.1		c.462A>G	p.Pro154Pro	synonymous	Exon 4 of 4	ENSP00000590157.1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67015 AN: 150740 Hom.: 16438 Cov.: 28

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.411

GnomAD2 exomes AF: 0.365 AC: 71414 AN: 195902 AF XY: 0.364

Gnomad AFR exome AF: 0.634

Gnomad AMR exome AF: 0.294

Gnomad ASJ exome AF: 0.200

Gnomad EAS exome AF: 0.757

Gnomad FIN exome AF: 0.346

Gnomad NFE exome AF: 0.258

Gnomad OTH exome AF: 0.327

GnomAD4 exome AF: 0.361 AC: 482330 AN: 1336628 Hom.: 107409 Cov.: 71 AF XY: 0.364 AC XY: 242104 AN XY: 665034

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

African (AFR) AF: 0.660 AC: 20792 AN: 31512

American (AMR) AF: 0.329 AC: 13094 AN: 39814

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 6390 AN: 24470

East Asian (EAS) AF: 0.721 AC: 27335 AN: 37926

South Asian (SAS) AF: 0.530 AC: 41520 AN: 78306

European-Finnish (FIN) AF: 0.378 AC: 19383 AN: 51280

Middle Eastern (MID) AF: 0.262 AC: 1447 AN: 5522

European-Non Finnish (NFE) AF: 0.327 AC: 331134 AN: 1011826

Other (OTH) AF: 0.379 AC: 21235 AN: 55972

⚠️ 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: 0.445 AC: 67117 AN: 150858 Hom.: 16481 Cov.: 28 AF XY: 0.448 AC XY: 33013 AN XY: 73648

African (AFR) AF: 0.640 AC: 26200 AN: 40922

American (AMR) AF: 0.365 AC: 5537 AN: 15152

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 934 AN: 3462

East Asian (EAS) AF: 0.714 AC: 3658 AN: 5126

South Asian (SAS) AF: 0.555 AC: 2630 AN: 4738

European-Finnish (FIN) AF: 0.384 AC: 4004 AN: 10430

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23022 AN: 67740

Other (OTH) AF: 0.410 AC: 856 AN: 2086

Alfa AF: 0.359 Hom.: 1889

Bravo AF: 0.449

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.1
DANN	Benign	0.56
PhyloP100		-2.2
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.8
Mutation Taster		=95/5	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: rs1057725; hg19: chr12-49522578; COSMIC: COSV60136046; COSMIC: COSV60136046;