chr22-50221368-G-A

Position:

• chr22-50221368-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_020461.4(TUBGCP6):​c.2991C>T​(p.Ser997Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00248 in 1,610,560 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0026 (8 hom.)
• Consequence: TUBGCP6 NM_020461.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.59

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]

TUBGCP6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 22-50221368-G-A is Benign according to our data. Variant chr22-50221368-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 437153.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-50221368-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-3.59 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00128 (195/152366) while in subpopulation NFE AF= 0.00232 (158/68028). AF 95% confidence interval is 0.00203. There are 0 homozygotes in gnomad4. There are 83 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBGCP6	NM_020461.4	c.2991C>T	p.Ser997Ser	synonymous_variant	16/25	ENST00000248846.10	NP_065194.3
TUBGCP6	XR_001755343.3	n.3555C>T		non_coding_transcript_exon_variant	16/20
TUBGCP6	XR_938347.3	n.3555C>T		non_coding_transcript_exon_variant	16/23
TUBGCP6	XR_007067982.1	n.3048+660C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBGCP6	ENST00000248846.10	c.2991C>T	p.Ser997Ser	synonymous_variant	16/25	1	NM_020461.4	ENSP00000248846.5
TUBGCP6	ENST00000439308.6	c.2991C>T	p.Ser997Ser	synonymous_variant	16/25	1		ENSP00000397387.2
TUBGCP6	ENST00000498611.5	n.3524C>T		non_coding_transcript_exon_variant	16/23	1
TUBGCP6	ENST00000491449.5	n.1298C>T		non_coding_transcript_exon_variant	8/16	5

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 194 AN: 152248 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000675

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00232

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00139 AC: 341 AN: 245920 Hom.: 0 AF XY: 0.00147 AC XY: 196 AN XY: 133402

Gnomad AFR exome AF: 0.000754

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000548

Gnomad SAS exome AF: 0.000262

Gnomad FIN exome AF: 0.0000530

Gnomad NFE exome AF: 0.00274

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.00260 AC: 3795 AN: 1458194 Hom.: 8 Cov.: 36 AF XY: 0.00257 AC XY: 1866 AN XY: 725486

Gnomad4 AFR exome AF: 0.000538

Gnomad4 AMR exome AF: 0.000157

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000348

Gnomad4 FIN exome AF: 0.000259

Gnomad4 NFE exome AF: 0.00327

Gnomad4 OTH exome AF: 0.00148

GnomAD4 genome AF: 0.00128 AC: 195 AN: 152366 Hom.: 0 Cov.: 34 AF XY: 0.00111 AC XY: 83 AN XY: 74508

Gnomad4 AFR AF: 0.000697

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00232

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00150 Hom.: 0

Bravo AF: 0.00136

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00240

EpiControl AF: 0.00273

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	TUBGCP6: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 04, 2024	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 22, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.18
DANN	Benign	0.47
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.2

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: rs143388326; hg19: chr22-50659797;