chr2-27356364-T-C

Variant names:

• chr2-27356364-T-C
• rs6760828
• ENST00000359541.6:c.-302A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000359541.6(GTF3C2):​c.-302A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 318,462 control chromosomes in the GnomAD database, including 31,529 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.46 (17709 hom., cov: 32)
  • Exomes 𝑓: 0.39 (13820 hom.)
• Consequence: GTF3C2 ENST00000359541.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.511
• Publications: 11 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-AS2 (HGNC:55699): (GTF3C2 antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000359541.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF3C2	NM_001035521.3	MANE Select	c.-25+375A>G		intron	N/A	NP_001030598.1
	GTF3C2	NM_001318909.4		c.-302A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	NP_001305838.2
	GTF3C2	NM_001394508.1		c.-54A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	NP_001381437.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF3C2	ENST00000359541.6	TSL:1	c.-302A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	ENSP00000352536.2
	GTF3C2	ENST00000359541.6	TSL:1	c.-302A>G		5_prime_UTR	Exon 1 of 19	ENSP00000352536.2
	GTF3C2	ENST00000264720.8	TSL:1 MANE Select	c.-25+375A>G		intron	N/A	ENSP00000264720.3

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70409 AN: 151932 Hom.: 17652 Cov.: 32

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.406

GnomAD4 exome AF: 0.393 AC: 65388 AN: 166414 Hom.: 13820 Cov.: 0 AF XY: 0.390 AC XY: 35899 AN XY: 92072

African (AFR) AF: 0.647 AC: 3181 AN: 4918

American (AMR) AF: 0.514 AC: 5545 AN: 10798

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1178 AN: 3434

East Asian (EAS) AF: 0.146 AC: 1189 AN: 8136

South Asian (SAS) AF: 0.398 AC: 14311 AN: 35996

European-Finnish (FIN) AF: 0.437 AC: 2972 AN: 6808

Middle Eastern (MID) AF: 0.333 AC: 185 AN: 556

European-Non Finnish (NFE) AF: 0.384 AC: 33700 AN: 87866

Other (OTH) AF: 0.396 AC: 3127 AN: 7902

GnomAD4 genome AF: 0.464 AC: 70539 AN: 152048 Hom.: 17709 Cov.: 32 AF XY: 0.463 AC XY: 34409 AN XY: 74324

African (AFR) AF: 0.655 AC: 27166 AN: 41484

American (AMR) AF: 0.468 AC: 7153 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1205 AN: 3472

East Asian (EAS) AF: 0.150 AC: 777 AN: 5174

South Asian (SAS) AF: 0.404 AC: 1947 AN: 4816

European-Finnish (FIN) AF: 0.448 AC: 4734 AN: 10570

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26333 AN: 67944

Other (OTH) AF: 0.410 AC: 861 AN: 2102

Alfa AF: 0.422 Hom.: 3402

Bravo AF: 0.473

Asia WGS AF: 0.348 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.1
DANN	Benign	0.68
PhyloP100		0.51
PromoterAI		-0.0013	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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: rs6760828; hg19: chr2-27579231;