dbSNP rs144693888: GTF3C4:p.Pro110Thr (chr9-132670926-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_012204.4(GTF3C4):c.328C>A(p.Pro110Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,536 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P110S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GTF3C4
NM_012204.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.51

Publications

0 publications found

Variant links:

Genes affected

GTF3C4 (HGNC:4667): (general transcription factor IIIC subunit 4) Predicted to enable enzyme activator activity. 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. Located in mitochondrion and nucleoplasm. Part of transcription factor TFIIIC complex. [provided by Alliance of Genome Resources, Apr 2022]

GTF3C4 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=0.25475788).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012204.4. 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
	GTF3C4	NM_012204.4	MANE Select	c.328C>A	p.Pro110Thr	missense	Exon 1 of 5	NP_036336.2	Q9UKN8
	GTF3C4	NR_133925.1		n.892C>A		non_coding_transcript_exon	Exon 1 of 6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GTF3C4	ENST00000372146.5	TSL:1 MANE Select	c.328C>A	p.Pro110Thr	missense	Exon 1 of 5	ENSP00000361219.4	Q9UKN8
GTF3C4	ENST00000898845.1		c.328C>A	p.Pro110Thr	missense	Exon 1 of 5	ENSP00000568904.1
GTF3C4	ENST00000483873.6	TSL:3	c.328C>A	p.Pro110Thr	missense	Exon 1 of 3	ENSP00000431378.1	F2Z356

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459536

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726112

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33458

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

86232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51954

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111256

Other (OTH)

AF:

0.00

AC:

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.650

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.83

M_CAP

Benign

0.079

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.8

PhyloP100

2.5

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-6.4

REVEL

Benign

0.15

Sift

Uncertain

0.0050

Sift4G

Benign

0.069

Polyphen

1.0

Vest4

0.55

MutPred

0.43

Gain of sheet (P = 0.0266)

MVP

0.76

MPC

0.89

ClinPred

0.98

GERP RS

3.6

PromoterAI

0.062

Neutral

(source)

Varity_R

0.21

gMVP

0.69

Mutation Taster

=77/23

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