2-27335616-G-C

Variant names:

• chr2-27335616-G-C
• rs771818393
• NM_001035521.3:c.1558C>G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001035521.3(GTF3C2):​c.1558C>G​(p.Leu520Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,550,082 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. 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. L520M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: GTF3C2 NM_001035521.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08

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

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17471284).
• BS2: High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF3C2	NM_001035521.3	c.1558C>G	p.Leu520Val	missense_variant	Exon 10 of 19	ENST00000264720.8	NP_001030598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF3C2	ENST00000264720.8	c.1558C>G	p.Leu520Val	missense_variant	Exon 10 of 19	1	NM_001035521.3	ENSP00000264720.3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152126 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000615 AC: 1 AN: 162612 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 85454

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000157

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000122 AC: 17 AN: 1397956 Hom.: 0 Cov.: 29 AF XY: 0.00000145 AC XY: 1 AN XY: 690116

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: 0.0000149

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152126 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74314

Gnomad4 AFR AF: 0.0000241

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: 0.0000294

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ExAC AF: 0.00000886 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T;T;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.66	.;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.2	L;L;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.40	N;N;.
REVEL	Benign	0.26
Sift	Benign	0.38	T;T;.
Sift4G	Benign	0.23	T;T;T
Polyphen		0.96	P;P;.
Vest4		0.14
MutPred		0.70		Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);
MVP		0.33
MPC		0.89
ClinPred		0.20	T
GERP RS		2.4
Varity_R		0.022
gMVP		0.42

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

Other links and lift over

dbSNP: rs771818393; hg19: chr2-27558483;