rs141805017

Variant names:

• chr22-50233406-C-T
• rs141805017
• NM_020461.4:c.1026G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-50233406-C-T
• chr22-50233406-C-A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS1

The NM_020461.4(TUBGCP6):​c.1026G>A​(p.Pro342Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000359 in 1,613,920 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00052 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00034 (1 hom.)
• Consequence: TUBGCP6 NM_020461.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: -4.22
• 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: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.03).
• BP6: Variant 22-50233406-C-T is Benign according to our data. Variant chr22-50233406-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 212503.
• BP7: Synonymous conserved (PhyloP=-4.22 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000519 (79/152316) while in subpopulation NFE AF = 0.000941 (64/68006). AF 95% confidence interval is 0.000756. There are 0 homozygotes in GnomAd4. There are 29 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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.1026G>A	p.Pro342Pro	synonymous	Exon 3 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.1026G>A	p.Pro342Pro	synonymous	Exon 3 of 25	ENSP00000248846.5	Q96RT7-1
	TUBGCP6	ENST00000439308.7	TSL:1	n.1026G>A		non_coding_transcript_exon	Exon 3 of 25	ENSP00000397387.2	E7EQL8
	TUBGCP6	ENST00000498611.5	TSL:1	n.1559G>A		non_coding_transcript_exon	Exon 3 of 23

Frequencies

GnomAD3 genomes AF: 0.000519 AC: 79 AN: 152198 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000941

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000455 AC: 114 AN: 250514 AF XY: 0.000317

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.000497

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000601

Gnomad NFE exome AF: 0.000769

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000342 AC: 500 AN: 1461604 Hom.: 1 Cov.: 32 AF XY: 0.000373 AC XY: 271 AN XY: 727102

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.000179 AC: 8 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.000344 AC: 9 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86238

European-Finnish (FIN) AF: 0.000769 AC: 41 AN: 53306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000383 AC: 426 AN: 1111906

Other (OTH) AF: 0.000199 AC: 12 AN: 60386

GnomAD4 genome AF: 0.000519 AC: 79 AN: 152316 Hom.: 0 Cov.: 33 AF XY: 0.000389 AC XY: 29 AN XY: 74462

African (AFR) AF: 0.0000962 AC: 4 AN: 41568

American (AMR) AF: 0.000131 AC: 2 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000941 AC: 64 AN: 68006

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000671 Hom.: 0

Bravo AF: 0.000366

EpiCase AF: 0.000600

EpiControl AF: 0.000534

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.63
DANN	Benign	0.76
PhyloP100		-4.2
Mutation Taster		=98/2	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

Other links and lift over

dbSNP: rs141805017; hg19: chr22-50671835; COSMIC: COSV50593705;