rs778386409

Variant names:

• chr22-50221059-A-G
• rs778386409
• NM_020461.4:c.3300T>C
• TUBGCP6 p.Thr1100Thr

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_020461.4(TUBGCP6):​c.3300T>C​(p.Thr1100Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00098 (0 hom., cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TUBGCP6 NM_020461.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.68
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• microcephaly and chorioretinopathy 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 22-50221059-A-G is Benign according to our data. Variant chr22-50221059-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 437150.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020461.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBGCP6	NM_020461.4	MANE Select	c.3300T>C	p.Thr1100Thr	synonymous	Exon 16 of 25	NP_065194.3	Q96RT7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBGCP6	ENST00000248846.10	TSL:1 MANE Select	c.3300T>C	p.Thr1100Thr	synonymous	Exon 16 of 25	ENSP00000248846.5	Q96RT7-1
	TUBGCP6	ENST00000439308.7	TSL:1	n.3300T>C		non_coding_transcript_exon	Exon 16 of 25	ENSP00000397387.2	E7EQL8
	TUBGCP6	ENST00000498611.5	TSL:1	n.3617+216T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000971 AC: 89 AN: 91700 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00144

Gnomad AMI AF: 0.00218

Gnomad AMR AF: 0.000933

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00185

Gnomad FIN AF: 0.000380

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000709

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 247326 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.07e-7 AC: 1 AN: 1414462 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 704286

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31478

American (AMR) AF: 0.0000237 AC: 1 AN: 42218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23712

East Asian (EAS) AF: 0.00 AC: 0 AN: 37154

South Asian (SAS) AF: 0.00 AC: 0 AN: 85248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5492

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080568

Other (OTH) AF: 0.00 AC: 0 AN: 56614

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000980 AC: 90 AN: 91794 Hom.: 0 Cov.: 31 AF XY: 0.000744 AC XY: 33 AN XY: 44342

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00147 AC: 34 AN: 23062

American (AMR) AF: 0.000931 AC: 8 AN: 8594

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 4 AN: 2314

East Asian (EAS) AF: 0.00135 AC: 4 AN: 2968

South Asian (SAS) AF: 0.00185 AC: 5 AN: 2702

European-Finnish (FIN) AF: 0.000380 AC: 2 AN: 5268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 94

European-Non Finnish (NFE) AF: 0.000709 AC: 32 AN: 45108

Other (OTH) AF: 0.00 AC: 0 AN: 1226

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0862 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.90
DANN	Benign	0.40
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs778386409;

hg19: chr22-50659488;

COSMIC: COSV50536223;

COSMIC: COSV50536223;