rs7424438

Positions:

• chr2-131479486-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000321253.7(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 ENST00000321253.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.965

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TUBA3D	NM_080386.4	c.375+30T>G		intron_variant		ENST00000321253.7	NP_525125.2
MZT2A	XM_005263742.4	c.320-7304A>C		intron_variant			XP_005263799.2
MZT2A	XM_047445568.1	c.623-7304A>C		intron_variant			XP_047301524.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBA3D	ENST00000321253.7	c.375+30T>G		intron_variant		1	NM_080386.4	ENSP00000326042	P1
MZT2A	ENST00000427024.5	c.279-7304A>C		intron_variant, NMD_transcript_variant		3		ENSP00000403353
TUBA3D	ENST00000409047.2	n.201+30T>G		intron_variant, non_coding_transcript_variant		2
MZT2A	ENST00000445782.2	n.331-7304A>C		intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes AF: 0.0581 AC: 13500 AN: 232406 Hom.: 1613 AF XY: 0.0531 AC XY: 6661 AN XY: 125524

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 SAS exome AF: 0.0479

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

Gnomad4 AFR exome AF: 0.402

Gnomad4 AMR exome AF: 0.0492

Gnomad4 ASJ exome AF: 0.0654

Gnomad4 EAS exome AF: 0.00134

Gnomad4 SAS exome AF: 0.0655

Gnomad4 FIN exome AF: 0.0506

Gnomad4 NFE exome AF: 0.0506

Gnomad4 OTH exome AF: 0.0729

GnomAD4 genome AF: 0.169 AC: 25594 AN: 151472 Hom.: 3936 Cov.: 32 AF XY: 0.164 AC XY: 12118 AN XY: 74052

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.0863

Gnomad4 ASJ AF: 0.0732

Gnomad4 EAS AF: 0.00463

Gnomad4 SAS AF: 0.0760

Gnomad4 FIN AF: 0.0500

Gnomad4 NFE AF: 0.0858

Gnomad4 OTH AF: 0.148

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

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: rs7424438; hg19: chr2-132237059; COSMIC: COSV58310824; COSMIC: COSV58310824;