22-50221071-A-G

Position:

• chr22-50221071-A-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The ENST00000248846.10(TUBGCP6):​c.3288T>C​(p.Asp1096=) variant causes a synonymous 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: 𝑓 0.000026 (0 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: TUBGCP6 ENST00000248846.10 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.18

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-7.18 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBGCP6	NM_020461.4	c.3288T>C	p.Asp1096=	synonymous_variant	16/25	ENST00000248846.10	NP_065194.3
TUBGCP6	XR_001755343.3	n.3852T>C		non_coding_transcript_exon_variant	16/20
TUBGCP6	XR_938347.3	n.3852T>C		non_coding_transcript_exon_variant	16/23
TUBGCP6	XR_007067982.1	n.3048+957T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBGCP6	ENST00000248846.10	c.3288T>C	p.Asp1096=	synonymous_variant	16/25	1	NM_020461.4	ENSP00000248846	P1
TUBGCP6	ENST00000439308.6	c.3288T>C	p.Asp1096=	synonymous_variant	16/25	1		ENSP00000397387
TUBGCP6	ENST00000498611.5	n.3617+204T>C		intron_variant, non_coding_transcript_variant		1
TUBGCP6	ENST00000491449.5	n.1595T>C		non_coding_transcript_exon_variant	8/16	5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 3 AN: 114014 Hom.: 0 Cov.: 33 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000343

Gnomad EAS AF: 0.000292

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000182

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 37

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000263 AC: 3 AN: 114100 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 55316

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000343

Gnomad4 EAS AF: 0.000292

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000182

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.36
DANN	Benign	0.24

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: rs6010209; hg19: chr22-50659500;