NM_017708.4:c.1232G>C

Variant names:

• chr19-48601314-C-G
• rs567457476
• NM_017708.4:c.1232G>C

Variant summary

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

The NM_017708.4(FAM83E):​c.1232G>C​(p.Arg411Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,416,714 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. R411W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: FAM83E NM_017708.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.79
• Publications: 0 publications found

Genes affected

FAM83E (HGNC:25972): (family with sequence similarity 83 member E) Enables protein kinase binding activity. Predicted to be involved in signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017708.4. 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
	FAM83E	NM_017708.4	MANE Select	c.1232G>C	p.Arg411Pro	missense	Exon 7 of 7	NP_060178.2	Q2M2I3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM83E	ENST00000263266.4	TSL:1 MANE Select	c.1232G>C	p.Arg411Pro	missense	Exon 7 of 7	ENSP00000263266.2	Q2M2I3
	FAM83E	ENST00000876133.1		c.1232G>C	p.Arg411Pro	missense	Exon 6 of 6	ENSP00000546192.1
	FAM83E	ENST00000876134.1		c.1232G>C	p.Arg411Pro	missense	Exon 6 of 6	ENSP00000546193.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416714 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 700702

African (AFR) AF: 0.00 AC: 0 AN: 32416

American (AMR) AF: 0.00 AC: 0 AN: 37500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25344

East Asian (EAS) AF: 0.00 AC: 0 AN: 37062

South Asian (SAS) AF: 0.00 AC: 0 AN: 81254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 9.19e-7 AC: 1 AN: 1088462

Other (OTH) AF: 0.00 AC: 0 AN: 58698

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.67	T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.8
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.23		Loss of helix (P = 0.0093)
MVP		0.39
MPC		1.1
ClinPred		0.94	D
GERP RS		4.0
Varity_R		0.40
gMVP		0.61
Mutation Taster		=60/40	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: rs567457476; hg19: chr19-49104571;