2-219250304-C-A

Variant names:

• chr2-219250304-C-A
• rs11556349
• NM_006000.3:c.*48G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006000.3(TUBA4A):​c.*48G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: TUBA4A NM_006000.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.930
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

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.*48G>T		3_prime_UTR	Exon 4 of 4	NP_005991.1	P68366-1
	STK16	NM_001330213.2	MANE Select	c.*1745C>A		3_prime_UTR	Exon 8 of 8	NP_001317142.1	O75716
	TUBA4A	NM_001278552.2		c.*48G>T		3_prime_UTR	Exon 4 of 4	NP_001265481.1	P68366-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBA4A	ENST00000248437.9	TSL:1 MANE Select	c.*48G>T		3_prime_UTR	Exon 4 of 4	ENSP00000248437.4	P68366-1
	STK16	ENST00000396738.7	TSL:2 MANE Select	c.*1745C>A		3_prime_UTR	Exon 8 of 8	ENSP00000379964.2	O75716
	STK16	ENST00000409638.7	TSL:1	c.*1745C>A		3_prime_UTR	Exon 8 of 8	ENSP00000386928.3	O75716

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 58

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.74
PhyloP100		-0.93

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: rs11556349; hg19: chr2-220115026;