Genetic Variant TUBGCP6:p.Met1178Leu (chr22-50220827-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020461.4(TUBGCP6):c.3532A>C(p.Met1178Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000155 in 1,289,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M1178V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TUBGCP6
NM_020461.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0290

Publications

1 publications found

Variant links:

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

TUBGCP6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043532908).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBGCP6	NM_020461.4	MANE Select	c.3532A>C	p.Met1178Leu	missense	Exon 16 of 25	NP_065194.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TUBGCP6	ENST00000248846.10	TSL:1 MANE Select	c.3532A>C	p.Met1178Leu	missense	Exon 16 of 25	ENSP00000248846.5
TUBGCP6	ENST00000439308.7	TSL:1	n.3532A>C		non_coding_transcript_exon	Exon 16 of 25	ENSP00000397387.2
TUBGCP6	ENST00000498611.5	TSL:1	n.3617+448A>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

84620

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000871

AC:

AN:

229718

AF XY:

0.00000798

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000130

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000155

AC:

AN:

1289336

Hom.:

Cov.:

AF XY:

0.00000312

AC XY:

AN XY:

641252

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27888

American (AMR)

AF:

0.00

AC:

AN:

36292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19240

East Asian (EAS)

AF:

0.0000836

AC:

AN:

23918

South Asian (SAS)

AF:

0.00

AC:

AN:

83122

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41956

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4912

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1003436

Other (OTH)

AF:

0.00

AC:

AN:

48572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

84688

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

41506

African (AFR)

AF:

0.00

AC:

AN:

21964

American (AMR)

AF:

0.00

AC:

AN:

8232

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2244

East Asian (EAS)

AF:

0.00

AC:

AN:

2302

South Asian (SAS)

AF:

0.00

AC:

AN:

2376

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4436

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

41416

Other (OTH)

AF:

0.00

AC:

AN:

1228

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.65

CADD

Benign

1.8

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.011

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.059

M_CAP

Benign

0.0065

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

PhyloP100

0.029

PrimateAI

Benign

0.31

PROVEAN

Benign

0.060

REVEL

Benign

0.015

Sift

Benign

0.38

Sift4G

Benign

0.14

Polyphen

0.0

Vest4

0.17

MutPred

0.32

Gain of helix (P = 0.1736)

MVP

0.11

MPC

0.10

ClinPred

0.012

GERP RS

1.2

PromoterAI

-0.040

Neutral

(source)

Varity_R

0.039

gMVP

0.19

Mutation Taster

=94/6

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over