rs7511006

Variant names:

• chr22-50237830-T-C
• rs7511006
• NM_020461.4:c.905+2374A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020461.4(TUBGCP6):​c.905+2374A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,092 control chromosomes in the GnomAD database, including 8,239 homozygotes. 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 0.31 (8239 hom., cov: 33)
• Consequence: TUBGCP6 NM_020461.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370
• Publications: 11 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: Labcorp Genetics (formerly Invitae), Orphanet, G2P, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBGCP6	NM_020461.4	c.905+2374A>G		intron_variant	Intron 2 of 24	ENST00000248846.10	NP_065194.3
TUBGCP6	XR_001755343.3	n.1469+2374A>G		intron_variant	Intron 2 of 19
TUBGCP6	XR_007067982.1	n.1469+2374A>G		intron_variant	Intron 2 of 18
TUBGCP6	XR_938347.3	n.1469+2374A>G		intron_variant	Intron 2 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBGCP6	ENST00000248846.10	c.905+2374A>G		intron_variant	Intron 2 of 24	1	NM_020461.4	ENSP00000248846.5
TUBGCP6	ENST00000439308.7	n.905+2374A>G		intron_variant	Intron 2 of 24	1		ENSP00000397387.2
TUBGCP6	ENST00000498611.5	n.1438+2374A>G		intron_variant	Intron 2 of 22	1
TUBGCP6	ENST00000434349.1	c.134+2395A>G		intron_variant	Intron 1 of 5	5		ENSP00000409650.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46985 AN: 151974 Hom.: 8241 Cov.: 33

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.302

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.309 AC: 46978 AN: 152092 Hom.: 8239 Cov.: 33 AF XY: 0.308 AC XY: 22941 AN XY: 74368

African (AFR) AF: 0.134 AC: 5578 AN: 41504

American (AMR) AF: 0.294 AC: 4502 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1237 AN: 3472

East Asian (EAS) AF: 0.334 AC: 1727 AN: 5166

South Asian (SAS) AF: 0.400 AC: 1926 AN: 4816

European-Finnish (FIN) AF: 0.377 AC: 3988 AN: 10584

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26956 AN: 67936

Other (OTH) AF: 0.298 AC: 630 AN: 2112

Alfa AF: 0.355 Hom.: 17471

Bravo AF: 0.291

Asia WGS AF: 0.304 AC: 1059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.52
PhyloP100		0.037
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7511006; hg19: chr22-50676259;