Genetic Variant GTF3C1:p.Glu1366Lys (chr16-27481179-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP5_ModerateBS2

The NM_001520.4(GTF3C1):c.4096G>A(p.Glu1366Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

GTF3C1
NM_001520.4 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 5.34

Publications

2 publications found

Variant links:

Genes affected

GTF3C1 (HGNC:4664): (general transcription factor IIIC subunit 1) Predicted to contribute to DNA binding activity. Predicted to be involved in 5S class rRNA transcription by RNA polymerase III and transcription initiation from RNA polymerase III promoter. Located in nucleolus and nucleoplasm. Part of transcription factor TFIIIC complex. [provided by Alliance of Genome Resources, Apr 2022]

GTF3C1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PP5

Variant 16-27481179-C-T is Pathogenic according to our data. Variant chr16-27481179-C-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 402157.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
GTF3C1	NM_001520.4 link	c.4096G>A	p.Glu1366Lys	missense_variant	Exon 27 of 37	ENST00000356183.9	NP_001511.2
GTF3C1	NM_001286242.2 link	c.4096G>A	p.Glu1366Lys	missense_variant	Exon 27 of 37		NP_001273171.1
GTF3C1	XM_017023188.3 link	c.3907G>A	p.Glu1303Lys	missense_variant	Exon 26 of 36		XP_016878677.1
GTF3C1	XM_047434036.1 link	c.3907G>A	p.Glu1303Lys	missense_variant	Exon 26 of 36		XP_047289992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF3C1	ENST00000356183.9 link	c.4096G>A	p.Glu1366Lys	missense_variant	Exon 27 of 37	1	NM_001520.4	ENSP00000348510.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461804

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

1111936

Other (OTH)

AF:

0.0000166

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

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

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Abnormal brain morphology

Pathogenic:1

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Uncertain

0.037

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

.;T

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.58

D;D

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.5

M;M

PhyloP100

5.3

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.90

N;N

REVEL

Benign

0.19

Sift

Benign

0.068

T;T

Sift4G

Benign

0.10

T;T

Polyphen

1.0

D;D

Vest4

0.56

MutPred

0.43

Gain of methylation at E1366 (P = 0.0172);Gain of methylation at E1366 (P = 0.0172);

MVP

0.18

MPC

1.1

ClinPred

0.90

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.57

Mutation Taster

=89/11

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over