NM_003203.5:c.1812+347C>A

Variant names:

• chr2-75679846-G-T
• rs4853169
• NM_003203.5:c.1812+347C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003203.5(GCFC2):​c.1812+347C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000393 in 254,568 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000039 (0 hom.)
• Consequence: GCFC2 NM_003203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257
• Publications: 0 publications found

Genes affected

GCFC2 (HGNC:1317): (GC-rich sequence DNA-binding factor 2) The first mRNA transcript isolated for this gene was part of an artificial chimera derived from two distinct gene transcripts and a primer used in the cloning process (see Genbank accession M29204). A positively charged amino terminus present only in the chimera was determined to bind GC-rich DNA, thus mistakenly thought to identify a transcription factor gene. [provided by RefSeq, Jul 2008]

LOC124906025 (HGNC:):

MRPL19 (HGNC:14052): (mitochondrial ribosomal protein L19) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCFC2	NM_003203.5	c.1812+347C>A		intron_variant	Intron 12 of 16	ENST00000321027.8	NP_003194.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCFC2	ENST00000321027.8	c.1812+347C>A		intron_variant	Intron 12 of 16	1	NM_003203.5	ENSP00000318690.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000393 AC: 1 AN: 254568 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 129206

African (AFR) AF: 0.00 AC: 0 AN: 7228

American (AMR) AF: 0.00 AC: 0 AN: 8216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9402

East Asian (EAS) AF: 0.00 AC: 0 AN: 23252

South Asian (SAS) AF: 0.00 AC: 0 AN: 3806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1314

European-Non Finnish (NFE) AF: 0.00000612 AC: 1 AN: 163406

Other (OTH) AF: 0.00 AC: 0 AN: 16772

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	10
DANN	Benign	0.69
PhyloP100		0.26

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: rs4853169; hg19: chr2-75906972;