rs7424438

Variant names:

• chr2-131479486-T-G
• rs7424438
• NM_080386.4:c.375+30T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080386.4(TUBA3D):​c.375+30T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0696 in 1,500,604 control chromosomes in the GnomAD database, including 11,571 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (3936 hom., cov: 32)
  • Exomes 𝑓: 0.058 (7635 hom.)
• Consequence: TUBA3D NM_080386.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.965
• Publications: 7 publications found

Genes affected

TUBA3D (HGNC:24071): (tubulin alpha 3d) This gene encodes a member of the alpha tubulin family. Tubulin is a major component of microtubules, which are composed of alpha- and beta-tubulin heterodimers and microtubule-associated proteins in the cytoskeleton. Microtubules maintain cellular structure, function in intracellular transport, and play a role in spindle formation during mitosis. [provided by RefSeq, Oct 2011]

MZT2A (HGNC:33187): (mitotic spindle organizing protein 2A) Located in centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBA3D	NM_080386.4	c.375+30T>G		intron_variant	Intron 3 of 4	ENST00000321253.7	NP_525125.2
MZT2A	XM_047445568.1	c.623-7304A>C		intron_variant	Intron 1 of 2		XP_047301524.1
MZT2A	XM_005263742.4	c.320-7304A>C		intron_variant	Intron 2 of 3		XP_005263799.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBA3D	ENST00000321253.7	c.375+30T>G		intron_variant	Intron 3 of 4	1	NM_080386.4	ENSP00000326042.6
TUBA3D	ENST00000409047.2	n.201+30T>G		intron_variant	Intron 2 of 2	2
MZT2A	ENST00000427024.5	n.278-7304A>C		intron_variant	Intron 2 of 4	3		ENSP00000403353.1
MZT2A	ENST00000445782.2	n.331-7304A>C		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25537 AN: 151360 Hom.: 3915 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.00462

Gnomad SAS AF: 0.0751

Gnomad FIN AF: 0.0500

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0858

Gnomad OTH AF: 0.149

GnomAD2 exomes AF: 0.0581 AC: 13500 AN: 232406 AF XY: 0.0531

Gnomad AFR exome AF: 0.373

Gnomad AMR exome AF: 0.0391

Gnomad ASJ exome AF: 0.0483

Gnomad EAS exome AF: 0.00191

Gnomad FIN exome AF: 0.0326

Gnomad NFE exome AF: 0.0440

Gnomad OTH exome AF: 0.0583

GnomAD4 exome AF: 0.0584 AC: 78801 AN: 1349132 Hom.: 7635 Cov.: 32 AF XY: 0.0585 AC XY: 39350 AN XY: 672228

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

African (AFR) AF: 0.402 AC: 10869 AN: 27030

American (AMR) AF: 0.0492 AC: 2138 AN: 43460

Ashkenazi Jewish (ASJ) AF: 0.0654 AC: 1654 AN: 25278

East Asian (EAS) AF: 0.00134 AC: 53 AN: 39534

South Asian (SAS) AF: 0.0655 AC: 5448 AN: 83236

European-Finnish (FIN) AF: 0.0506 AC: 2674 AN: 52830

Middle Eastern (MID) AF: 0.0863 AC: 473 AN: 5482

European-Non Finnish (NFE) AF: 0.0506 AC: 51377 AN: 1015848

Other (OTH) AF: 0.0729 AC: 4115 AN: 56434

⚠️ 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: 0.169 AC: 25594 AN: 151472 Hom.: 3936 Cov.: 32 AF XY: 0.164 AC XY: 12118 AN XY: 74052

African (AFR) AF: 0.413 AC: 16912 AN: 40912

American (AMR) AF: 0.0863 AC: 1315 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 254 AN: 3468

East Asian (EAS) AF: 0.00463 AC: 24 AN: 5180

South Asian (SAS) AF: 0.0760 AC: 366 AN: 4814

European-Finnish (FIN) AF: 0.0500 AC: 530 AN: 10594

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0858 AC: 5832 AN: 67956

Other (OTH) AF: 0.148 AC: 312 AN: 2104

Alfa AF: 0.115 Hom.: 415

Bravo AF: 0.185

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.53
DANN	Benign	0.82
PhyloP100		-0.96
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: rs7424438; hg19: chr2-132237059; COSMIC: COSV58310824; COSMIC: COSV58310824;