rs60154251

Variant names:

• chr2-130191918-G-A
• rs60154251
• NM_207312.3:c.1266C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-130191918-G-A
• chr2-130191918-G-C
• chr2-130191918-G-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_207312.3(TUBA3E):​c.1266C>T​(p.Arg422Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,610,554 control chromosomes in the GnomAD database, including 127,171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11808 hom., cov: 30)
  • Exomes 𝑓: 0.40 (115363 hom.)
• Consequence: TUBA3E NM_207312.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.08
• Publications: 13 publications found

Genes affected

TUBA3E (HGNC:20765): (tubulin alpha 3e) Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulin. The genes encoding these microtubule constituents are part of the tubulin superfamily, which is composed of six distinct families. Genes from the alpha, beta and gamma tubulin families are found in all eukaryotes. The alpha and beta tubulins represent the major components of microtubules, while gamma tubulin plays a critical role in the nucleation of microtubule assembly. This gene encodes an alpha tubulin that highly conserved among species. A missense mutation in this gene has been potentially linked to microlissencephaly and global developmental delay. [provided by RefSeq, Jul 2016]

MZT2B (HGNC:25886): (mitotic spindle organizing protein 2B) Located in cytosol; microtubule cytoskeleton; and nucleoplasm. Part of gamma-tubulin large complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-130191918-G-A is Benign according to our data. Variant chr2-130191918-G-A is described in ClinVar as Benign. ClinVar VariationId is 767820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.08 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207312.3. 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
	TUBA3E	NM_207312.3	MANE Select	c.1266C>T	p.Arg422Arg	synonymous	Exon 5 of 5	NP_997195.2	Q6PEY2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBA3E	ENST00000312988.9	TSL:1 MANE Select	c.1266C>T	p.Arg422Arg	synonymous	Exon 5 of 5	ENSP00000318197.7	Q6PEY2

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59194 AN: 151458 Hom.: 11805 Cov.: 30

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.379

GnomAD2 exomes AF: 0.407 AC: 101925 AN: 250706 AF XY: 0.406

Gnomad AFR exome AF: 0.341

Gnomad AMR exome AF: 0.452

Gnomad ASJ exome AF: 0.333

Gnomad EAS exome AF: 0.464

Gnomad FIN exome AF: 0.396

Gnomad NFE exome AF: 0.401

Gnomad OTH exome AF: 0.416

GnomAD4 exome AF: 0.396 AC: 578044 AN: 1458976 Hom.: 115363 Cov.: 80 AF XY: 0.395 AC XY: 286491 AN XY: 725246

African (AFR) AF: 0.341 AC: 11403 AN: 33438

American (AMR) AF: 0.455 AC: 20264 AN: 44542

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 8643 AN: 26018

East Asian (EAS) AF: 0.419 AC: 16595 AN: 39652

South Asian (SAS) AF: 0.405 AC: 34825 AN: 85970

European-Finnish (FIN) AF: 0.397 AC: 21164 AN: 53294

Middle Eastern (MID) AF: 0.364 AC: 2093 AN: 5748

European-Non Finnish (NFE) AF: 0.396 AC: 439243 AN: 1110066

Other (OTH) AF: 0.395 AC: 23814 AN: 60248

GnomAD4 genome AF: 0.391 AC: 59225 AN: 151578 Hom.: 11808 Cov.: 30 AF XY: 0.393 AC XY: 29125 AN XY: 74022

African (AFR) AF: 0.350 AC: 14455 AN: 41286

American (AMR) AF: 0.470 AC: 7156 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1172 AN: 3466

East Asian (EAS) AF: 0.463 AC: 2368 AN: 5120

South Asian (SAS) AF: 0.411 AC: 1964 AN: 4782

European-Finnish (FIN) AF: 0.386 AC: 4049 AN: 10494

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26966 AN: 67894

Other (OTH) AF: 0.380 AC: 800 AN: 2108

Alfa AF: 0.386 Hom.: 3630

Bravo AF: 0.395

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	-0.82
CADD	Benign	2.4
DANN	Benign	0.86
PhyloP100		-1.1
Mutation Taster		=100/0	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: rs60154251; hg19: chr2-130949491; COSMIC: COSV56059034; COSMIC: COSV56059034;