rs540957245

Variant names:

• chr22-50217770-C-G
• NM_020461.4:c.5426G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-50217770-C-G
• chr22-50217770-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020461.4(TUBGCP6):​c.5426G>C​(p.Arg1809Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TUBGCP6 NM_020461.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.02

Genes affected

TUBGCP6 (HGNC:18127): (tubulin gamma complex component 6) The protein encoded by this gene is part of a large multisubunit complex required for microtubule nucleation at the centrosome. [provided by RefSeq, Jul 2008]

SELENOO (HGNC:30395): (selenoprotein O) This gene encodes a selenoprotein that is localized to the mitochondria. It is the largest mammalian selenoprotein, containing the rare amino acid selenocysteine (Sec). Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. The exact function of this selenoprotein is not known, but it is thought to have redox activity. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.881

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBGCP6	NM_020461.4	c.5426G>C	p.Arg1809Pro	missense_variant	Exon 25 of 25	ENST00000248846.10	NP_065194.3
SELENOO	NM_031454.2	c.*401C>G		downstream_gene_variant		ENST00000380903.7	NP_113642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBGCP6	ENST00000248846.10	c.5426G>C	p.Arg1809Pro	missense_variant	Exon 25 of 25	1	NM_020461.4	ENSP00000248846.5
SELENOO	ENST00000380903.7	c.*401C>G		downstream_gene_variant		1	NM_031454.2	ENSP00000370288.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461758 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727174

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.88	D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-5.0	D;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.018	D;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.54	P;.
Vest4		0.70
MutPred		0.80		Loss of helix (P = 0.1299);.;
MVP		0.50
MPC		0.62
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.92
gMVP		0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-50656199;