dbSNP rs144769462: GTF3C2:p.Ser776Phe (chr2-27328119-G-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_001035521.3(GTF3C2):c.2327C>T(p.Ser776Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,456,712 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GTF3C2
NM_001035521.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.50

Publications

0 publications found

Variant links:

Genes affected

GTF3C2 (HGNC:4665): (general transcription factor IIIC subunit 2) Contributes to DNA binding activity. Involved in transcription by RNA polymerase III. Located in nucleoplasm. Part of transcription factor TFIIIC complex. [provided by Alliance of Genome Resources, Apr 2022]

GTF3C2 links:

Genome browser will be placed here

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=0.21732235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF3C2	NM_001035521.3 link	c.2327C>T	p.Ser776Phe	missense_variant	Exon 17 of 19	ENST00000264720.8	NP_001030598.1	Q8WUA4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GTF3C2	ENST00000264720.8 link	c.2327C>T	p.Ser776Phe	missense_variant	Exon 17 of 19	1	NM_001035521.3	ENSP00000264720.3	Q8WUA4-1
GTF3C2	ENST00000415683.2 link	n.*49C>T		non_coding_transcript_exon_variant	Exon 5 of 6	5		ENSP00000414422.2	H7C3X9
GTF3C2	ENST00000415683.2 link	n.*49C>T		3_prime_UTR_variant	Exon 5 of 6	5		ENSP00000414422.2	H7C3X9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000804

AC:

AN:

248728

AF XY:

0.00000743

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1456712

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724966

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33186

American (AMR)

AF:

0.00

AC:

AN:

43814

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26062

East Asian (EAS)

AF:

0.00

AC:

AN:

39646

South Asian (SAS)

AF:

0.00

AC:

AN:

85724

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1108956

Other (OTH)

AF:

0.00

AC:

AN:

60174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 13, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2327C>T (p.S776F) alteration is located in exon 18 (coding exon 16) of the GTF3C2 gene. This alteration results from a C to T substitution at nucleotide position 2327, causing the serine (S) at amino acid position 776 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.0063

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

T;T

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.80

.;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

0.34

N;N

PhyloP100

4.5

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.24

Sift

Benign

0.067

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.98

D;D

Vest4

0.19

MVP

0.23

MPC

0.36

ClinPred

0.47

GERP RS

5.2

PromoterAI

0.0074

Neutral

(source)

Varity_R

0.085

gMVP

0.56

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over