Variant 2-27341958-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001035521.3(GTF3C2):c.845C>T(p.Ser282Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000021 ( 0 hom. )

Consequence

GTF3C2
NM_001035521.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.39

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:

GTF3C2-AS1 (HGNC:40269): (GTF3C2 antisense RNA 1)

GTF3C2-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19290492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GTF3C2	NM_001035521.3 linkuse as main transcript	c.845C>T	p.Ser282Phe	missense_variant	4/19	ENST00000264720.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GTF3C2	ENST00000264720.8 linkuse as main transcript	c.845C>T	p.Ser282Phe	missense_variant	4/19	1	NM_001035521.3	P1	Q8WUA4-1
GTF3C2-AS1	ENST00000590383.4 linkuse as main transcript	n.484-85G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461392

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726978

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.845C>T (p.S282F) alteration is located in exon 5 (coding exon 3) of the GTF3C2 gene. This alteration results from a C to T substitution at nucleotide position 845, causing the serine (S) at amino acid position 282 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

0.096

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;T;T

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.063

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

1.1

L;L;.

MutationTaster

Benign

0.92

N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.74

N;N;.

REVEL

Benign

0.13

Sift

Uncertain

0.025

D;D;.

Sift4G

Uncertain

0.038

D;D;D

Polyphen

0.57

P;P;.

Vest4

0.17

MutPred

0.28

Loss of phosphorylation at S282 (P = 0.0062);Loss of phosphorylation at S282 (P = 0.0062);Loss of phosphorylation at S282 (P = 0.0062);

MVP

0.19

MPC

0.37

ClinPred

0.64

GERP RS

5.2

Varity_R

0.070

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over