20-35286643-G-T

Position:

• chr20-35286643-G-T

Variant summary

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

The NM_178468.6(FAM83C):​c.2136C>A​(p.Asp712Glu) 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. 15/21 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)
• Consequence: FAM83C NM_178468.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.180

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 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=0.06429383).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM83C	NM_178468.6	c.2136C>A	p.Asp712Glu	missense_variant	4/4	ENST00000374408.4	NP_848563.1
FAM83C	XM_047439892.1	c.1608C>A	p.Asp536Glu	missense_variant	4/4		XP_047295848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM83C	ENST00000374408.4	c.2136C>A	p.Asp712Glu	missense_variant	4/4	1	NM_178468.6	ENSP00000363529.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

May 23, 2024

The c.2136C>A (p.D712E) alteration is located in exon 4 (coding exon 4) of the FAM83C gene. This alteration results from a C to A substitution at nucleotide position 2136, causing the aspartic acid (D) at amino acid position 712 to be replaced by a glutamic acid (E). 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	0.13
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.1
DANN	Benign	0.96
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.070
Sift	Uncertain	0.016	D
Sift4G	Benign	0.19	T
Polyphen		0.0080	B
Vest4		0.023
MutPred		0.16		Gain of sheet (P = 0.0125);
MVP		0.44
MPC		0.17
ClinPred		0.093	T
GERP RS		3.5
Varity_R		0.099
gMVP		0.15

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: chr20-33874446;