20-59025600-G-C

Position:

• chr20-59025600-G-C

Variant summary

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

The NM_030773.4(TUBB1):​c.*817G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,172 control chromosomes in the GnomAD database, including 1,770 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 0.13 (1770 hom., cov: 33)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: TUBB1 NM_030773.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

Genes affected

TUBB1 (HGNC:16257): (tubulin beta 1 class VI) This gene encodes a member of the beta tubulin protein family. Beta tubulins are one of two core protein families (alpha and beta tubulins) that heterodimerize and assemble to form microtubules. This protein is specifically expressed in platelets and megakaryocytes and may be involved in proplatelet production and platelet release. A mutations in this gene is associated with autosomal dominant macrothrombocytopenia. Two pseudogenes of this gene are found on chromosome Y.[provided by RefSeq, Jul 2010]

ATP5F1E (HGNC:838): (ATP synthase F1 subunit epsilon) This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel consists of three main subunits (a, b, c). This gene encodes the epsilon subunit of the catalytic core. Two pseudogenes of this gene are located on chromosomes 4 and 13. Read-through transcripts that include exons from this gene are expressed from the upstream gene SLMO2.[provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBB1	NM_030773.4	c.*817G>C		3_prime_UTR_variant	4/4	ENST00000217133.2	NP_110400.1
ATP5F1E	NM_006886.4	c.*3245C>G		3_prime_UTR_variant	3/3	ENST00000243997.8	NP_008817.1
TUBB1	XM_017028085.2	c.*817G>C		3_prime_UTR_variant	4/4		XP_016883574.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBB1	ENST00000217133.2	c.*817G>C		3_prime_UTR_variant	4/4	1	NM_030773.4	ENSP00000217133.1
ATP5F1E	ENST00000243997.8	c.*3245C>G		3_prime_UTR_variant	3/3	1	NM_006886.4	ENSP00000243997.3

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20448 AN: 152050 Hom.: 1765 Cov.: 33

Gnomad AFR AF: 0.0341

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.135 AC: 20471 AN: 152168 Hom.: 1770 Cov.: 33 AF XY: 0.135 AC XY: 10042 AN XY: 74394

Gnomad4 AFR AF: 0.0340

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.155

Alfa AF: 0.151 Hom.: 288

Bravo AF: 0.132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10485828; hg19: chr20-57600655;