Genetic Variant GTF3C5:p.Gly140Ser (chr9-133043772-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_012087.4(GTF3C5):c.418G>A(p.Gly140Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000204 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

GTF3C5
NM_012087.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.19

Publications

0 publications found

Variant links:

Genes affected

GTF3C5 (HGNC:4668): (general transcription factor IIIC subunit 5) Predicted to contribute to DNA binding activity. Predicted to be involved in 5S class rRNA transcription by RNA polymerase III and tRNA transcription by RNA polymerase III. Predicted to act upstream of or within skeletal muscle cell differentiation. Located in nucleoplasm. Part of transcription factor TFIIIC complex. [provided by Alliance of Genome Resources, Apr 2022]

GTF3C5 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: MODERATE, LIMITED Submitted by: G2P, Ambry Genetics

GTF3C5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26817048).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012087.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GTF3C5	NM_012087.4	MANE Select	c.418G>A	p.Gly140Ser	missense	Exon 3 of 11	NP_036219.2	Q9Y5Q8-1
GTF3C5	NM_001122823.2		c.418G>A	p.Gly140Ser	missense	Exon 3 of 12	NP_001116295.1	Q9Y5Q8-3
GTF3C5	NM_001286709.2		c.51-7011G>A		intron	N/A	NP_001273638.1	H7BY84

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GTF3C5	ENST00000372097.10	TSL:1 MANE Select	c.418G>A	p.Gly140Ser	missense	Exon 3 of 11	ENSP00000361169.5	Q9Y5Q8-1
GTF3C5	ENST00000372108.9	TSL:1	c.418G>A	p.Gly140Ser	missense	Exon 3 of 12	ENSP00000361180.5	Q9Y5Q8-3
GTF3C5	ENST00000916424.1		c.361G>A	p.Gly121Ser	missense	Exon 3 of 12	ENSP00000586483.1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251454

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

1111994

Other (OTH)

AF:

0.0000497

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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

AF:

0.0000591

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41442

American (AMR)

AF:

0.000131

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000141

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.053

Eigen

Benign

0.12

Eigen_PC

Benign

0.078

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.81

M_CAP

Benign

0.017

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.8

PhyloP100

5.2

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.2

REVEL

Benign

0.17

Sift

Benign

0.10

Sift4G

Benign

0.27

Polyphen

0.98

Vest4

0.36

MVP

0.58

MPC

0.79

ClinPred

0.77

GERP RS

3.2

Varity_R

0.14

gMVP

0.60

Mutation Taster

=71/29

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over