dbSNP rs1239917299: GTF3C6:p.Phe133Leu (chr6-110967547-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138408.4(GTF3C6):c.399C>A(p.Phe133Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GTF3C6
NM_138408.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.977

Publications

0 publications found

Variant links:

Genes affected

GTF3C6 (HGNC:20872): (general transcription factor IIIC subunit 6) RNA polymerases are unable to initiate RNA synthesis in the absence of additional proteins called general transcription factors (GTFs). GTFs assemble in a complex on the DNA promoter and recruit the RNA polymerase. GTF3C family proteins (e.g., GTF3C1, MIM 603246) are essential for RNA polymerase III to make a number of small nuclear and cytoplasmic RNAs, including 5S RNA (MIM 180420), tRNA, and adenovirus-associated (VA) RNA of both cellular and viral origin.[supplied by OMIM, Mar 2008]

GTF3C6 links:

ENSG00000298854 (HGNC:):

ENSG00000298854 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16965574).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138408.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF3C6	NM_138408.4	MANE Select	c.399C>A	p.Phe133Leu	missense	Exon 6 of 6	NP_612417.1	Q969F1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GTF3C6	ENST00000329970.8	TSL:1 MANE Select	c.399C>A	p.Phe133Leu	missense	Exon 6 of 6	ENSP00000357863.4	Q969F1
GTF3C6	ENST00000935770.1		c.537C>A	p.Phe179Leu	missense	Exon 7 of 7	ENSP00000605829.1
GTF3C6	ENST00000935771.1		c.456C>A	p.Phe152Leu	missense	Exon 6 of 6	ENSP00000605830.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461366

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726976

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39672

South Asian (SAS)

AF:

0.00

AC:

AN:

86214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5600

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111796

Other (OTH)

AF:

0.00

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.84

M_CAP

Benign

0.0078

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

0.98

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.37

Sift

Uncertain

0.028

Sift4G

Benign

0.11

Polyphen

0.17

Vest4

0.46

MutPred

0.42

Gain of sheet (P = 0.0827)

MVP

0.095

MPC

0.47

ClinPred

0.89

GERP RS

2.5

Varity_R

0.10

gMVP

0.21

Mutation Taster

=81/19

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