Variant 2-27327280-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001035521.3(GTF3C2):c.2414C>T(p.Ser805Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,380,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

GTF3C2
NM_001035521.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.65

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30891392).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF3C2	NM_001035521.3 link	c.2414C>T	p.Ser805Leu	missense_variant	18/19	ENST00000264720.8	NP_001030598.1	Q8WUA4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GTF3C2	ENST00000264720.8 link	c.2414C>T	p.Ser805Leu	missense_variant	18/19	1	NM_001035521.3	ENSP00000264720.3	Q8WUA4-1
GTF3C2	ENST00000415683.2 link	n.*136C>T		non_coding_transcript_exon_variant	6/6	5		ENSP00000414422.2	H7C3X9
GTF3C2	ENST00000415683.2 link	n.*136C>T		3_prime_UTR_variant	6/6	5		ENSP00000414422.2	H7C3X9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000416

AC:

AN:

240612

Hom.:

AF XY:

0.00000768

AC XY:

AN XY:

130284

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 SAS exome

AF:

0.0000348

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.24e-7

AC:

AN:

1380634

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689392

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:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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 02, 2024

The c.2414C>T (p.S805L) alteration is located in exon 19 (coding exon 17) of the GTF3C2 gene. This alteration results from a C to T substitution at nucleotide position 2414, causing the serine (S) at amino acid position 805 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

0.15

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;T

Eigen

Benign

-0.049

Eigen_PC

Benign

-0.0040

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.85

.;D

M_CAP

Benign

0.036

MetaRNN

Benign

0.31

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.1

L;L

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.20

Sift

Benign

0.045

D;D

Sift4G

Uncertain

0.027

D;D

Polyphen

0.79

P;P

Vest4

0.45

MutPred

0.40

Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);

MVP

0.24

MPC

0.15

ClinPred

0.33

GERP RS

4.0

Varity_R

0.062

gMVP

0.63

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

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