dbSNP rs1680152177: GTF3C2:p.Pro766Ser (chr2-27328150-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001035521.3(GTF3C2):c.2296C>T(p.Pro766Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GTF3C2
NM_001035521.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.720

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:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050048172).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF3C2	NM_001035521.3 link	c.2296C>T	p.Pro766Ser	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.2296C>T	p.Pro766Ser	missense_variant	Exon 17 of 19	1	NM_001035521.3	ENSP00000264720.3	Q8WUA4-1
GTF3C2	ENST00000415683.2 link	n.*18C>T		non_coding_transcript_exon_variant	Exon 5 of 6	5		ENSP00000414422.2	H7C3X9
GTF3C2	ENST00000415683.2 link	n.*18C>T		3_prime_UTR_variant	Exon 5 of 6	5		ENSP00000414422.2	H7C3X9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1452210

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722764

African (AFR)

AF:

0.00

AC:

AN:

32776

American (AMR)

AF:

0.00

AC:

AN:

41720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25878

East Asian (EAS)

AF:

0.00

AC:

AN:

39650

South Asian (SAS)

AF:

0.00

AC:

AN:

84804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108248

Other (OTH)

AF:

0.00

AC:

AN:

60022

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 20, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2296C>T (p.P766S) 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 2296, causing the proline (P) at amino acid position 766 to be replaced by a serine (S). 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

0.069

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.091

T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.64

.;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.050

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

PhyloP100

0.72

PrimateAI

Benign

0.29

PROVEAN

Benign

0.10

N;N

REVEL

Benign

0.036

Sift

Benign

0.36

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.0050

B;B

Vest4

0.043

MutPred

0.32

Loss of loop (P = 0.0112);Loss of loop (P = 0.0112);

MVP

0.12

MPC

0.16

ClinPred

0.033

GERP RS

1.9

Varity_R

0.020

gMVP

0.49

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