Genetic Variant NM_001035521.3:c.2321C>A (chr2-27328125-G-T) – 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.2321C>A(p.Ala774Asp) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A774V) has been classified 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

Not reported in ClinVar

Conservation

PhyloP100: 1.45

Publications

2 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: 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=0.10889846).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001035521.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GTF3C2	NM_001035521.3	MANE Select	c.2321C>A	p.Ala774Asp	missense	Exon 17 of 19	NP_001030598.1	Q8WUA4-1
GTF3C2	NM_001318909.4		c.2321C>A	p.Ala774Asp	missense	Exon 17 of 19	NP_001305838.2	Q8WUA4-1
GTF3C2	NM_001388380.3		c.2321C>A	p.Ala774Asp	missense	Exon 18 of 20	NP_001375309.2	Q8WUA4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GTF3C2	ENST00000264720.8	TSL:1 MANE Select	c.2321C>A	p.Ala774Asp	missense	Exon 17 of 19	ENSP00000264720.3	Q8WUA4-1
GTF3C2	ENST00000359541.6	TSL:1	c.2321C>A	p.Ala774Asp	missense	Exon 17 of 19	ENSP00000352536.2	Q8WUA4-1
GTF3C2	ENST00000454704.5	TSL:1	c.845C>A	p.Ala282Asp	missense	Exon 8 of 10	ENSP00000393429.1	H0Y4Q6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1456336

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724760

African (AFR)

AF:

0.00

AC:

AN:

33178

American (AMR)

AF:

0.00

AC:

AN:

43804

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26068

East Asian (EAS)

AF:

0.00

AC:

AN:

39636

South Asian (SAS)

AF:

0.00

AC:

AN:

85720

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108586

Other (OTH)

AF:

0.00

AC:

AN:

60186

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.69

M_CAP

Benign

0.021

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

1.5

PrimateAI

Benign

0.34

PROVEAN

Benign

1.2

REVEL

Benign

0.27

Sift

Benign

0.45

Sift4G

Uncertain

0.040

Polyphen

0.75

Vest4

0.20

MutPred

0.17

Gain of sheet (P = 0.0101)

MVP

0.33

MPC

0.29

ClinPred

0.37

GERP RS

4.2

PromoterAI

-0.011

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.083

gMVP

0.64

Mutation Taster

=95/5

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over