rs777166372

Variant names:

• chr2-75670170-G-A
• rs777166372
• NM_003203.5:c.2071C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-75670170-G-A
• chr2-75670170-G-C
• chr2-75670170-G-T

Variant summary

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

The NM_003203.5(GCFC2):​c.2071C>T​(p.Pro691Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,454,736 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: GCFC2 NM_003203.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.38
• 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]

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]

ENSG00000271452 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCFC2	NM_003203.5	MANE Select	c.2071C>T	p.Pro691Ser	missense	Exon 15 of 17	NP_003194.3
	GCFC2	NM_001410845.1		c.1957C>T	p.Pro653Ser	missense	Exon 15 of 17	NP_001397774.1	P16383-2
	GCFC2	NM_001201334.2		c.1564C>T	p.Pro522Ser	missense	Exon 15 of 17	NP_001188263.1	B3KUM5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCFC2	ENST00000321027.8	TSL:1 MANE Select	c.2071C>T	p.Pro691Ser	missense	Exon 15 of 17	ENSP00000318690.3	P16383-1
	GCFC2	ENST00000470197.5	TSL:1	n.1413C>T		non_coding_transcript_exon	Exon 11 of 13
	GCFC2	ENST00000884726.1		c.2095C>T	p.Pro699Ser	missense	Exon 15 of 17	ENSP00000554785.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000254 AC: 37 AN: 1454736 Hom.: 0 Cov.: 27 AF XY: 0.0000235 AC XY: 17 AN XY: 724112

African (AFR) AF: 0.00 AC: 0 AN: 33336

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.000328 AC: 13 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 86056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000217 AC: 24 AN: 1105594

Other (OTH) AF: 0.00 AC: 0 AN: 60148

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		3.4
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.25
Sift	Benign	0.43	T
Sift4G	Uncertain	0.031	D
Polyphen		1.0	D
Vest4		0.29
MutPred		0.52		Gain of glycosylation at P691 (P = 0.085)
MVP		0.67
MPC		0.47
ClinPred		0.98	D
GERP RS		4.7
PromoterAI		-0.031	Neutral
Varity_R		0.066
gMVP		0.29
Mutation Taster		=87/13	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: rs777166372; hg19: chr2-75897296;