2-27337932-T-C

Variant names:

• chr2-27337932-T-C
• NM_001035521.3:c.944A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001035521.3(GTF3C2):​c.944A>G​(p.Lys315Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 7.0e-7 (0 hom.)
• Consequence: GTF3C2 NM_001035521.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.88
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2651242).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF3C2	NM_001035521.3	MANE Select	c.944A>G	p.Lys315Arg	missense	Exon 5 of 19	NP_001030598.1	Q8WUA4-1
	GTF3C2	NM_001318909.4		c.944A>G	p.Lys315Arg	missense	Exon 5 of 19	NP_001305838.2	Q8WUA4-1
	GTF3C2	NM_001388380.3		c.944A>G	p.Lys315Arg	missense	Exon 6 of 20	NP_001375309.2	Q8WUA4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF3C2	ENST00000264720.8	TSL:1 MANE Select	c.944A>G	p.Lys315Arg	missense	Exon 5 of 19	ENSP00000264720.3	Q8WUA4-1
	GTF3C2	ENST00000359541.6	TSL:1	c.944A>G	p.Lys315Arg	missense	Exon 5 of 19	ENSP00000352536.2	Q8WUA4-1
	GTF3C2	ENST00000957129.1		c.944A>G	p.Lys315Arg	missense	Exon 5 of 19	ENSP00000627188.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432226 Hom.: 0 Cov.: 27 AF XY: 0.00000140 AC XY: 1 AN XY: 714412

African (AFR) AF: 0.00 AC: 0 AN: 32926

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25980

East Asian (EAS) AF: 0.00 AC: 0 AN: 39540

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1084914

Other (OTH) AF: 0.00 AC: 0 AN: 59380

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.27	T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.9
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.82	N
REVEL	Uncertain	0.30
Sift	Benign	0.40	T
Sift4G	Benign	0.30	T
Polyphen		0.96	P
Vest4		0.27
MutPred		0.60		Loss of helix (P = 0.0068)
MVP		0.38
MPC		1.4
ClinPred		0.75	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.057
gMVP		0.34
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

hg19: chr2-27560799;