chr2-27326854-C-T

Variant names:

• chr2-27326854-C-T
• rs1680091419
• NM_001035521.3:c.2557G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001035521.3(GTF3C2):​c.2557G>A​(p.Val853Ile) 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. V853L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GTF3C2 NM_001035521.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• 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]

ACMG classification

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=0.24725848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF3C2	NM_001035521.3	c.2557G>A	p.Val853Ile	missense_variant	Exon 19 of 19	ENST00000264720.8	NP_001030598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF3C2	ENST00000264720.8	c.2557G>A	p.Val853Ile	missense_variant	Exon 19 of 19	1	NM_001035521.3	ENSP00000264720.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	T;T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.70	.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.0	L;L
PhyloP100		1.8
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.45	N;N
REVEL	Benign	0.063
Sift	Benign	0.14	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.90	P;P
Vest4		0.20
MutPred		0.25		Loss of glycosylation at S858 (P = 0.1759);Loss of glycosylation at S858 (P = 0.1759);
MVP		0.12
MPC		0.13
ClinPred		0.46	T
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.071
gMVP		0.35
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs1680091419; hg19: chr2-27549721; COSMIC: COSV51991197; COSMIC: COSV51991197;