NM_178468.6:c.863G>C

Variant names:

• chr20-35287916-C-G
• rs193920940
• NM_178468.6:c.863G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_178468.6(FAM83C):​c.863G>C​(p.Arg288Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000285 in 1,403,862 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R288H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: FAM83C NM_178468.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 0 publications found

Genes affected

FAM83C (HGNC:16121): (family with sequence similarity 83 member C) This gene encodes a member of the family with sequence similarity 83 protein family. The encoded protein may be involved in regulating MAPK signaling in cancer cells. [provided by RefSeq, Mar 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM83C	NM_178468.6	c.863G>C	p.Arg288Pro	missense_variant	Exon 4 of 4	ENST00000374408.4	NP_848563.1
FAM83C	XM_047439892.1	c.335G>C	p.Arg112Pro	missense_variant	Exon 4 of 4		XP_047295848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM83C	ENST00000374408.4	c.863G>C	p.Arg288Pro	missense_variant	Exon 4 of 4	1	NM_178468.6	ENSP00000363529.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000285 AC: 4 AN: 1403862 Hom.: 0 Cov.: 34 AF XY: 0.00000289 AC XY: 2 AN XY: 692828

African (AFR) AF: 0.00 AC: 0 AN: 31888

American (AMR) AF: 0.00 AC: 0 AN: 36166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25220

East Asian (EAS) AF: 0.00 AC: 0 AN: 36174

South Asian (SAS) AF: 0.00 AC: 0 AN: 79678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 9.25e-7 AC: 1 AN: 1081210

Other (OTH) AF: 0.0000516 AC: 3 AN: 58176

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	T
Eigen	Benign	0.063
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.3
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.24
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.058	T
Polyphen		1.0	D
Vest4		0.59
MutPred		0.66		Loss of sheet (P = 0.0181);
MVP		0.53
MPC		0.88
ClinPred		0.89	D
GERP RS		3.4
Varity_R		0.43
gMVP		0.71
Mutation Taster		=74/26	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: rs193920940; hg19: chr20-33875719;