rs61739385

Positions:

• chr22-50221052-G-A
• chr22-50221052-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_020461.4(TUBGCP6):​c.3307C>T​(p.Arg1103Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00149 in 1,612,410 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0078 (15 hom., cov: 34)
  • Exomes 𝑓: 0.00084 (14 hom.)
• Consequence: TUBGCP6 NM_020461.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 4.24

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0074418485).
• BP6: Variant 22-50221052-G-A is Benign according to our data. Variant chr22-50221052-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 445785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-50221052-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00777 (1177/151468) while in subpopulation AFR AF= 0.0272 (1119/41122). AF 95% confidence interval is 0.0259. There are 15 homozygotes in gnomad4. There are 571 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBGCP6	NM_020461.4	c.3307C>T	p.Arg1103Trp	missense_variant	16/25	ENST00000248846.10	NP_065194.3
TUBGCP6	XR_001755343.3	n.3871C>T		non_coding_transcript_exon_variant	16/20
TUBGCP6	XR_938347.3	n.3871C>T		non_coding_transcript_exon_variant	16/23
TUBGCP6	XR_007067982.1	n.3048+976C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBGCP6	ENST00000248846.10	c.3307C>T	p.Arg1103Trp	missense_variant	16/25	1	NM_020461.4	ENSP00000248846.5
TUBGCP6	ENST00000439308.6	c.3307C>T	p.Arg1103Trp	missense_variant	16/25	1		ENSP00000397387.2
TUBGCP6	ENST00000498611.5	n.3617+223C>T		intron_variant		1
TUBGCP6	ENST00000491449.5	n.1614C>T		non_coding_transcript_exon_variant	8/16	5

Frequencies

GnomAD3 genomes AF: 0.00776 AC: 1175 AN: 151352 Hom.: 15 Cov.: 34

Gnomad AFR AF: 0.0272

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00237

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00626

GnomAD3 exomes AF: 0.00191 AC: 481 AN: 251452 Hom.: 5 AF XY: 0.00129 AC XY: 175 AN XY: 135908

Gnomad AFR exome AF: 0.0261

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000527

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000840 AC: 1227 AN: 1460942 Hom.: 14 Cov.: 37 AF XY: 0.000722 AC XY: 525 AN XY: 726806

Gnomad4 AFR exome AF: 0.0286

Gnomad4 AMR exome AF: 0.00144

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000675

Gnomad4 OTH exome AF: 0.00184

GnomAD4 genome AF: 0.00777 AC: 1177 AN: 151468 Hom.: 15 Cov.: 34 AF XY: 0.00771 AC XY: 571 AN XY: 74020

Gnomad4 AFR AF: 0.0272

Gnomad4 AMR AF: 0.00236

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00619

Alfa AF: 0.00196 Hom.: 2

Bravo AF: 0.00886

ESP6500AA AF: 0.0238 AC: 105

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00248 AC: 301

EpiCase AF: 0.000327

EpiControl AF: 0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Apr 19, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.19	T;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.93	D;D
MetaRNN	Benign	0.0074	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	D;.
Vest4		0.50
MVP		0.59
MPC		0.54
ClinPred		0.036	T
GERP RS		4.9
Varity_R		0.14
gMVP		0.40

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: rs61739385; hg19: chr22-50659481; COSMIC: COSV99030488; COSMIC: COSV99030488;