rs193920940

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr20-35287916-C-A
• chr20-35287916-C-G
• chr20-35287916-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_178468.6(FAM83C):​c.863G>T​(p.Arg288Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,403,862 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict 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: 7.1e-7 (0 hom.)
• Consequence: FAM83C NM_178468.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

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

Verdict is Uncertain_significance. Variant got 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>T	p.Arg288Leu	missense_variant	Exon 4 of 4	ENST00000374408.4	NP_848563.1
FAM83C	XM_047439892.1	c.335G>T	p.Arg112Leu	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>T	p.Arg288Leu	missense_variant	Exon 4 of 4	1	NM_178468.6	ENSP00000363529.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1403862 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 692828

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.25e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.061
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.23
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.037	D
Polyphen		0.91	P
Vest4		0.49
MutPred		0.61		Loss of sheet (P = 0.007);
MVP		0.48
MPC		0.71
ClinPred		0.92	D
GERP RS		3.4
Varity_R		0.19
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-33875719;