rs724159997

Variant names:

• chr22-50221196-G-A
• rs724159997
• NM_020461.4:c.3163C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 2 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: Uncertain_significance. The variant received 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 VariationId is 162406.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBGCP6	NM_020461.4	c.3163C>T	p.His1055Tyr	missense_variant	Exon 16 of 25	ENST00000248846.10	NP_065194.3
TUBGCP6	XR_001755343.3	n.3727C>T		non_coding_transcript_exon_variant	Exon 16 of 20
TUBGCP6	XR_938347.3	n.3727C>T		non_coding_transcript_exon_variant	Exon 16 of 23
TUBGCP6	XR_007067982.1	n.3048+832C>T		intron_variant	Intron 15 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBGCP6	ENST00000248846.10	c.3163C>T	p.His1055Tyr	missense_variant	Exon 16 of 25	1	NM_020461.4	ENSP00000248846.5
TUBGCP6	ENST00000439308.7	n.3163C>T		non_coding_transcript_exon_variant	Exon 16 of 25	1		ENSP00000397387.2
TUBGCP6	ENST00000498611.5	n.3617+79C>T		intron_variant	Intron 16 of 22	1
TUBGCP6	ENST00000491449.5	n.1470C>T		non_coding_transcript_exon_variant	Exon 8 of 16	5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251474 AF XY: 0.00000736

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: 0.00000879

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

African (AFR) AF: 0.00 AC: 0 AN: 33410

American (AMR) AF: 0.00 AC: 0 AN: 44408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1107118

Other (OTH) AF: 0.00 AC: 0 AN: 60162

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

Dec 01, 2014

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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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;.
PhyloP100		5.0
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
Mutation Taster		=29/71	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs724159997; hg19: chr22-50659625;