rs35231253

Variant names:

• chr22-50218105-C-T
• rs35231253
• NM_020461.4:c.5181G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-50218105-C-T
• chr22-50218105-C-A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The ENST00000425018.1(TUBGCP6):​c.1195-7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,612,486 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0068 (13 hom., cov: 33)
  • Exomes 𝑓: 0.00072 (13 hom.)
• Consequence: TUBGCP6 ENST00000425018.1 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.34
• Publications: 1 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), ClinGen, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 22-50218105-C-T is Benign according to our data. Variant chr22-50218105-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 212515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00678 (1032/152182) while in subpopulation AFR AF = 0.0235 (977/41532). AF 95% confidence interval is 0.0223. There are 13 homozygotes in GnomAd4. There are 495 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000425018.1. 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.5181G>A	p.Thr1727Thr	synonymous	Exon 24 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.5181G>A	p.Thr1727Thr	synonymous	Exon 24 of 25	ENSP00000248846.5	Q96RT7-1
	TUBGCP6	ENST00000425018.1	TSL:1	c.1195-7G>A		splice_region intron	N/A	ENSP00000405979.1	H7C2H5
	TUBGCP6	ENST00000439308.7	TSL:1	n.*758G>A		non_coding_transcript_exon	Exon 24 of 25	ENSP00000397387.2	E7EQL8

Frequencies

GnomAD3 genomes AF: 0.00677 AC: 1030 AN: 152062 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

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: 0.000147

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00173 AC: 430 AN: 248998 AF XY: 0.00116

Gnomad AFR exome AF: 0.0238

Gnomad AMR exome AF: 0.000985

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000476

Gnomad NFE exome AF: 0.0000711

Gnomad OTH exome AF: 0.000986

GnomAD4 exome AF: 0.000723 AC: 1056 AN: 1460304 Hom.: 13 Cov.: 36 AF XY: 0.000626 AC XY: 455 AN XY: 726470

African (AFR) AF: 0.0252 AC: 843 AN: 33474

American (AMR) AF: 0.00127 AC: 57 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52244

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5766

European-Non Finnish (NFE) AF: 0.0000396 AC: 44 AN: 1111696

Other (OTH) AF: 0.00164 AC: 99 AN: 60364

GnomAD4 genome AF: 0.00678 AC: 1032 AN: 152182 Hom.: 13 Cov.: 33 AF XY: 0.00665 AC XY: 495 AN XY: 74402

African (AFR) AF: 0.0235 AC: 977 AN: 41532

American (AMR) AF: 0.00196 AC: 30 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67978

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00563 Hom.: 6

Bravo AF: 0.00763

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.58
DANN	Benign	0.89
PhyloP100		-3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.44		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.44		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs35231253; hg19: chr22-50656534;