20-35286540-A-G

Position:

• chr20-35286540-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178468.6(FAM83C):​c.2239T>C​(p.Ser747Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FAM83C NM_178468.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.02

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16370529).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM83C	NM_178468.6	c.2239T>C	p.Ser747Pro	missense_variant	4/4	ENST00000374408.4	NP_848563.1
FAM83C	XM_047439892.1	c.1711T>C	p.Ser571Pro	missense_variant	4/4		XP_047295848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM83C	ENST00000374408.4	c.2239T>C	p.Ser747Pro	missense_variant	4/4	1	NM_178468.6	ENSP00000363529.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455094 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 723254

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Apr 01, 2024

The c.2239T>C (p.S747P) alteration is located in exon 4 (coding exon 4) of the FAM83C gene. This alteration results from a T to C substitution at nucleotide position 2239, causing the serine (S) at amino acid position 747 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
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.083
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.011	D
Polyphen		0.63	P
Vest4		0.29
MutPred		0.35		Loss of phosphorylation at S747 (P = 9e-04);
MVP		0.15
MPC		0.57
ClinPred		0.77	D
GERP RS		0.86
Varity_R		0.22
gMVP		0.14

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: chr20-33874343;