dbSNP rs369941156: GTF3C2:p.Pro366Ser (chr2-27337275-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001035521.3(GTF3C2):c.1096C>T(p.Pro366Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,612,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

GTF3C2
NM_001035521.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.88

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:

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

GTF3C2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03174925).

BS2

High AC in GnomAd4 at 26 AD gene.

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.1096C>T	p.Pro366Ser	missense	Exon 7 of 19	NP_001030598.1	Q8WUA4-1
GTF3C2	NM_001318909.4		c.1096C>T	p.Pro366Ser	missense	Exon 7 of 19	NP_001305838.2	Q8WUA4-1
GTF3C2	NM_001388380.3		c.1096C>T	p.Pro366Ser	missense	Exon 8 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.1096C>T	p.Pro366Ser	missense	Exon 7 of 19	ENSP00000264720.3	Q8WUA4-1
GTF3C2	ENST00000359541.6	TSL:1	c.1096C>T	p.Pro366Ser	missense	Exon 7 of 19	ENSP00000352536.2	Q8WUA4-1
GTF3C2	ENST00000957129.1		c.1096C>T	p.Pro366Ser	missense	Exon 7 of 19	ENSP00000627188.1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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

GnomAD2 exomes

AF:

0.0000358

AC:

AN:

251070

AF XY:

0.0000368

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1460220

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

726542

show subpopulations

African (AFR)

AF:

0.000568

AC:

AN:

33430

American (AMR)

AF:

0.0000224

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86180

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000270

AC:

AN:

1110594

Other (OTH)

AF:

0.0000497

AC:

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000171

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.000555

AC:

AN:

41432

American (AMR)

AF:

0.000131

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000197

Hom.:

Bravo

AF:

0.000196

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.092

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.74

M_CAP

Benign

0.025

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.1

PhyloP100

1.9

PrimateAI

Benign

0.43

PROVEAN

Benign

0.79

REVEL

Benign

0.10

Sift

Benign

0.57

Sift4G

Uncertain

0.048

Polyphen

0.0010

Vest4

0.073

MVP

0.082

MPC

0.86

ClinPred

0.042

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.031

gMVP

0.42

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over