20-35287167-C-T

Variant names:

• chr20-35287167-C-T
• rs200282148
• NM_178468.6:c.1612G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_178468.6(FAM83C):​c.1612G>A​(p.Glu538Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000212 in 1,606,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: FAM83C NM_178468.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0660
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.042572588).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178468.6. 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
	FAM83C	NM_178468.6	MANE Select	c.1612G>A	p.Glu538Lys	missense	Exon 4 of 4	NP_848563.1	Q9BQN1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM83C	ENST00000374408.4	TSL:1 MANE Select	c.1612G>A	p.Glu538Lys	missense	Exon 4 of 4	ENSP00000363529.3	Q9BQN1

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152172 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000248 AC: 60 AN: 241542 AF XY: 0.000220

Gnomad AFR exome AF: 0.0000673

Gnomad AMR exome AF: 0.0000582

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000570

Gnomad NFE exome AF: 0.000490

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000217 AC: 315 AN: 1454480 Hom.: 0 Cov.: 34 AF XY: 0.000187 AC XY: 135 AN XY: 723810

African (AFR) AF: 0.00 AC: 0 AN: 33402

American (AMR) AF: 0.0000448 AC: 2 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26020

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86150

European-Finnish (FIN) AF: 0.0000423 AC: 2 AN: 47290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.000270 AC: 300 AN: 1111310

Other (OTH) AF: 0.000116 AC: 7 AN: 60270

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152172 Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16 AN XY: 74344

African (AFR) AF: 0.0000241 AC: 1 AN: 41448

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000198 Hom.: 1

Bravo AF: 0.000162

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000388 AC: 47

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

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	0.082
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	10
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.066
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.083
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.062	T
Polyphen		0.48	P
Vest4		0.13
MVP		0.25
MPC		0.21
ClinPred		0.060	T
GERP RS		3.2
Varity_R		0.11
gMVP		0.082
Mutation Taster		=99/1	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: rs200282148; hg19: chr20-33874970; COSMIC: COSV106110480; COSMIC: COSV106110480;