chr2-130191938-C-T

Position:

• chr2-130191938-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_207312.3(TUBA3E):​c.1246G>A​(p.Gly416Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0022 in 1,614,070 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0020 (19 hom.)
• Consequence: TUBA3E NM_207312.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.19

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:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.025752872).
• BP6: Variant 2-130191938-C-T is Benign according to our data. Variant chr2-130191938-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2651365.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00205 (2995/1461868) while in subpopulation MID AF= 0.0322 (186/5768). AF 95% confidence interval is 0.0285. There are 19 homozygotes in gnomad4_exome. There are 1633 alleles in male gnomad4_exome subpopulation. Median coverage is 74. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBA3E	NM_207312.3	c.1246G>A	p.Gly416Arg	missense_variant	5/5	ENST00000312988.9
MZT2B	XM_047445914.1	c.319+9163C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBA3E	ENST00000312988.9	c.1246G>A	p.Gly416Arg	missense_variant	5/5	1	NM_207312.3	P1

Frequencies

GnomAD3 genomes AF: 0.00368 AC: 560 AN: 152084 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.00572

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00223

Gnomad OTH AF: 0.00575

GnomAD3 exomes AF: 0.00290 AC: 730 AN: 251466 Hom.: 7 AF XY: 0.00315 AC XY: 428 AN XY: 135902

Gnomad AFR exome AF: 0.00566

Gnomad AMR exome AF: 0.00237

Gnomad ASJ exome AF: 0.0126

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00320

Gnomad FIN exome AF: 0.000508

Gnomad NFE exome AF: 0.00258

Gnomad OTH exome AF: 0.00424

GnomAD4 exome AF: 0.00205 AC: 2995 AN: 1461868 Hom.: 19 Cov.: 74 AF XY: 0.00225 AC XY: 1633 AN XY: 727232

Gnomad4 AFR exome AF: 0.00505

Gnomad4 AMR exome AF: 0.00255

Gnomad4 ASJ exome AF: 0.0130

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00314

Gnomad4 FIN exome AF: 0.000300

Gnomad4 NFE exome AF: 0.00149

Gnomad4 OTH exome AF: 0.00402

GnomAD4 genome AF: 0.00369 AC: 562 AN: 152202 Hom.: 4 Cov.: 31 AF XY: 0.00392 AC XY: 292 AN XY: 74418

Gnomad4 AFR AF: 0.00573

Gnomad4 AMR AF: 0.00451

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00456

Gnomad4 FIN AF: 0.000753

Gnomad4 NFE AF: 0.00224

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00399 Hom.: 2

Bravo AF: 0.00389

ESP6500AA AF: 0.00477 AC: 21

ESP6500EA AF: 0.00396 AC: 34

ExAC AF: 0.00301 AC: 366

EpiCase AF: 0.00333

EpiControl AF: 0.00433

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

TUBA3E: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Pathogenic	0.18
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.026	T
MetaSVM	Uncertain	0.59	D
MutationAssessor	Pathogenic	3.9	H
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Pathogenic	0.76
Sift4G	Uncertain	0.028	D
Polyphen		1.0	D
Vest4		0.74
MutPred		0.48		Gain of solvent accessibility (P = 0.0306);
MVP		0.89
ClinPred		0.065	T
GERP RS		3.0
Varity_R		0.75
gMVP		0.54

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: rs138838108; hg19: chr2-130949511;