1-161595561-A-C

Position:

• chr1-161595561-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000466542.6(FCGR2C):​c.769A>C​(p.Thr257Pro) 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. 9/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T257S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 29)
• Consequence: FCGR2C ENST00000466542.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.841

Genes affected

FCGR2C (HGNC:15626): (Fc gamma receptor IIc (gene/pseudogene)) This gene encodes one of three members of a family of low-affinity immunoglobulin gamma Fc receptors found on the surface of many immune response cells. The encoded protein is a transmembrane glycoprotein and may be involved in phagocytosis and clearing of immune complexes. An allelic polymorphism in this gene results in both coding and non-coding variants. [provided by RefSeq, Apr 2012]

ENSG00000289768 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061757207).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCGR2C	NR_047648.1	n.868A>C		non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCGR2C	ENST00000466542.6	c.769A>C	p.Thr257Pro	missense_variant	6/7	1		ENSP00000426627.1
ENSG00000289768	ENST00000699402.1	c.40+35494T>G		intron_variant				ENSP00000514363.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

The c.769A>C (p.T257P) alteration is located in exon 6 (coding exon 6) of the FCGR2C gene. This alteration results from a A to C substitution at nucleotide position 769, causing the threonine (T) at amino acid position 257 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	0.81
DANN	Benign	0.62
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0095	N
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.0	T
REVEL	Benign	0.049
Vest4		0.051
MVP		0.014
ClinPred		0.082	T
GERP RS		-2.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-161565351;