22-50219736-G-C

Variant names:

• chr22-50219736-G-C
• NM_020461.4:c.4223C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020461.4(TUBGCP6):​c.4223C>G​(p.Ala1408Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TUBGCP6 NM_020461.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12793204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBGCP6	NM_020461.4	c.4223C>G	p.Ala1408Gly	missense_variant	Exon 18 of 25	ENST00000248846.10	NP_065194.3
TUBGCP6	XR_001755343.3	n.4846C>G		non_coding_transcript_exon_variant	Exon 18 of 20
TUBGCP6	XR_007067982.1	n.3163C>G		non_coding_transcript_exon_variant	Exon 17 of 19
TUBGCP6	XR_938347.3	n.4787C>G		non_coding_transcript_exon_variant	Exon 18 of 23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBGCP6	ENST00000248846.10	c.4223C>G	p.Ala1408Gly	missense_variant	Exon 18 of 25	1	NM_020461.4	ENSP00000248846.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461442 Hom.: 0 Cov.: 76 AF XY: 0.00000275 AC XY: 2 AN XY: 727054

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.28
DANN	Benign	0.70
DEOGEN2	Benign	0.012	T;.
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.23	T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.90	L;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.27	N;N
REVEL	Benign	0.025
Sift	Benign	0.29	T;T
Sift4G	Benign	0.25	T;T
Polyphen		0.0060	B;.
Vest4		0.18
MutPred		0.39		Gain of relative solvent accessibility (P = 0.0215);.;
MVP		0.30
MPC		0.13
ClinPred		0.16	T
GERP RS		-4.2
Varity_R		0.031
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr22-50658165;