NM_006000.3:c.1143G>A

Variant names:

• chr2-219250556-C-T
• rs757609748
• NM_006000.3:c.1143G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_006000.3(TUBA4A):​c.1143G>A​(p.Thr381Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,614,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: TUBA4A NM_006000.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.158
• Publications: 0 publications found

Genes affected

TUBA4A (HGNC:12407): (tubulin alpha 4a) 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. There are multiple alpha and beta tubulin genes and they are highly conserved among and between species. This gene encodes an alpha tubulin that is a highly conserved homolog of a rat testis-specific alpha tubulin. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2013]

STK16 (HGNC:11394): (serine/threonine kinase 16) Predicted to enable protein serine/threonine kinase activity. Involved in protein autophosphorylation. Located in cytosol; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 2-219250556-C-T is Benign according to our data. Variant chr2-219250556-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1176422.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.158 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 15 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006000.3. 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
	TUBA4A	NM_006000.3	MANE Select	c.1143G>A	p.Thr381Thr	synonymous	Exon 4 of 4	NP_005991.1	P68366-1
	TUBA4A	NM_001278552.2		c.1098G>A	p.Thr366Thr	synonymous	Exon 4 of 4	NP_001265481.1	P68366-2
	STK16	NM_001330213.2	MANE Select	c.*1997C>T		downstream_gene	N/A	NP_001317142.1	O75716

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBA4A	ENST00000248437.9	TSL:1 MANE Select	c.1143G>A	p.Thr381Thr	synonymous	Exon 4 of 4	ENSP00000248437.4	P68366-1
	TUBA4A	ENST00000875456.1		c.1149G>A	p.Thr383Thr	synonymous	Exon 4 of 4	ENSP00000545515.1
	TUBA4A	ENST00000392088.6	TSL:2	c.1098G>A	p.Thr366Thr	synonymous	Exon 4 of 4	ENSP00000375938.2	P68366-2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000278 AC: 7 AN: 251442 AF XY: 0.0000294

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000719 AC: 8 AN: 1112012

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152178 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74324

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.1
DANN	Benign	0.88
PhyloP100		-0.16
Mutation Taster		=85/15	polymorphism

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: rs757609748; hg19: chr2-220115278;