chr20-59025600-G-C

Variant names:

• chr20-59025600-G-C
• rs10485828
• NM_030773.4:c.*817G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

ATP5F1E Gene-Disease associations (from GenCC):

• mitochondrial proton-transporting ATP synthase complex deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial complex V (ATP synthase) deficiency, nuclear type 3

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030773.4. 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
	TUBB1	NM_030773.4	MANE Select	c.*817G>C		3_prime_UTR	Exon 4 of 4	NP_110400.1
	ATP5F1E	NM_006886.4	MANE Select	c.*3245C>G		3_prime_UTR	Exon 3 of 3	NP_008817.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBB1	ENST00000217133.2	TSL:1 MANE Select	c.*817G>C		3_prime_UTR	Exon 4 of 4	ENSP00000217133.1
	ATP5F1E	ENST00000243997.8	TSL:1 MANE Select	c.*3245C>G		3_prime_UTR	Exon 3 of 3	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0340 AC: 1411 AN: 41528

American (AMR) AF: 0.154 AC: 2353 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 560 AN: 3468

East Asian (EAS) AF: 0.159 AC: 821 AN: 5176

South Asian (SAS) AF: 0.191 AC: 922 AN: 4830

European-Finnish (FIN) AF: 0.144 AC: 1525 AN: 10576

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12291 AN: 67990

Other (OTH) AF: 0.155 AC: 327 AN: 2112

Alfa AF: 0.151 Hom.: 288

Bravo AF: 0.132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.76
PhyloP100		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs10485828; hg19: chr20-57600655;