chr2-75665954-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003203.5(GCFC2):c.2203C>T(p.His735Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000229 in 1,593,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

GCFC2
NM_003203.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.87

Publications

3 publications found

Variant links:

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]

GCFC2 links:

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]

MRPL19 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.12904322).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003203.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GCFC2	NM_003203.5	MANE Select	c.2203C>T	p.His735Tyr	missense	Exon 16 of 17	NP_003194.3
GCFC2	NM_001410845.1		c.2089C>T	p.His697Tyr	missense	Exon 16 of 17	NP_001397774.1	P16383-2
GCFC2	NM_001201334.2		c.1696C>T	p.His566Tyr	missense	Exon 16 of 17	NP_001188263.1	B3KUM5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GCFC2	ENST00000321027.8	TSL:1 MANE Select	c.2203C>T	p.His735Tyr	missense	Exon 16 of 17	ENSP00000318690.3	P16383-1
GCFC2	ENST00000470197.5	TSL:1	n.1545C>T		non_coding_transcript_exon	Exon 12 of 13
GCFC2	ENST00000884726.1		c.2227C>T	p.His743Tyr	missense	Exon 16 of 17	ENSP00000554785.1

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000121

AC:

AN:

247416

AF XY:

0.0000896

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000180

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000552

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000204

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000233

AC:

336

AN:

1441474

Hom.:

Cov.:

AF XY:

0.000231

AC XY:

166

AN XY:

718188

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32906

American (AMR)

AF:

0.000136

AC:

AN:

44012

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25892

East Asian (EAS)

AF:

0.00158

AC:

AN:

39258

South Asian (SAS)

AF:

0.00

AC:

AN:

85094

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53178

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.000235

AC:

258

AN:

1095730

Other (OTH)

AF:

0.000167

AC:

AN:

59730

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000191

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41440

American (AMR)

AF:

0.000393

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

68032

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000201

Hom.:

Bravo

AF:

0.000185

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000824

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.17

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.60

M_CAP

Benign

0.0082

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

1.9

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.085

Sift

Benign

0.20

Sift4G

Benign

0.23

Polyphen

0.60

Vest4

0.10

MVP

0.55

MPC

0.10

ClinPred

0.090

GERP RS

5.0

Varity_R

0.14

gMVP

0.32

Mutation Taster

=83/17

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over