Variant 2-27342175-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001035521.3(GTF3C2):c.628G>T(p.Val210Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GTF3C2
NM_001035521.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.36

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034386247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GTF3C2	NM_001035521.3 linkuse as main transcript	c.628G>T	p.Val210Leu	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.628G>T	p.Val210Leu	missense_variant	4/19	1	NM_001035521.3	P1	Q8WUA4-1
GTF3C2-AS1	ENST00000590383.4 linkuse as main transcript	n.616C>A		non_coding_transcript_exon_variant	4/4	5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727228

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2023

The c.628G>T (p.V210L) alteration is located in exon 5 (coding exon 3) of the GTF3C2 gene. This alteration results from a G to T substitution at nucleotide position 628, causing the valine (V) at amino acid position 210 to be replaced by a leucine (L). 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

0.095

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.11

T;T;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.39

M_CAP

Benign

0.034

MetaRNN

Benign

0.034

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.16

N;N;.

REVEL

Benign

0.083

Sift

Benign

0.46

T;T;.

Sift4G

Benign

0.54

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.035

MutPred

0.13

Gain of glycosylation at P209 (P = 0.1022);Gain of glycosylation at P209 (P = 0.1022);Gain of glycosylation at P209 (P = 0.1022);

MVP

0.12

MPC

0.13

ClinPred

0.12

GERP RS

4.5

Varity_R

0.024

gMVP

0.071

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over