rs724159997

chr22-50221196-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_020461.4(TUBGCP6):c.3163C>T(p.His1055Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,456,000 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. H1055H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TUBGCP6 NM_020461.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.04

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 22-50221196-G-A is Pathogenic according to our data. Variant chr22-50221196-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 162406.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-50221196-G-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBGCP6	NM_020461.4	c.3163C>T	p.His1055Tyr	missense_variant	16/25	ENST00000248846.10
TUBGCP6	XR_001755343.3	n.3727C>T		non_coding_transcript_exon_variant	16/20
TUBGCP6	XR_938347.3	n.3727C>T		non_coding_transcript_exon_variant	16/23
TUBGCP6	XR_007067982.1	n.3048+832C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBGCP6	ENST00000248846.10	c.3163C>T	p.His1055Tyr	missense_variant	16/25	1	NM_020461.4	P1
TUBGCP6	ENST00000439308.6	c.3163C>T	p.His1055Tyr	missense_variant	16/25	1
TUBGCP6	ENST00000498611.5	n.3617+79C>T		intron_variant, non_coding_transcript_variant		1
TUBGCP6	ENST00000491449.5	n.1470C>T		non_coding_transcript_exon_variant	8/16	5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251474 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135916

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1456000 Hom.: 0 Cov.: 36 AF XY: 0.00000276 AC XY: 2 AN XY: 724374

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Microcephaly and chorioretinopathy 1 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.0090	T
BayesDel_noAF	Benign	-0.25
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.24	T;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T;T
M_CAP	Pathogenic	0.37	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.23
Sift	Benign	0.084	T;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.99	D;.
Vest4		0.31
MutPred		0.47		Loss of disorder (P = 0.0372);Loss of disorder (P = 0.0372);
MVP		0.45
MPC		0.52
ClinPred		0.91	D
GERP RS		4.1
Varity_R		0.14
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs724159997; hg19: chr22-50659625;