chr19-48603504-C-T

Variant names:

• chr19-48603504-C-T
• rs199701408
• NM_017708.4:c.1166G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017708.4(FAM83E):​c.1166G>A​(p.Gly389Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,414,428 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. 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. G389A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: FAM83E NM_017708.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.685
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0937722).

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.1166G>A	p.Gly389Glu	missense	Exon 6 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.1166G>A	p.Gly389Glu	missense	Exon 6 of 7	ENSP00000263266.2	Q2M2I3
	FAM83E	ENST00000876133.1		c.1166G>A	p.Gly389Glu	missense	Exon 5 of 6	ENSP00000546192.1
	FAM83E	ENST00000876134.1		c.1166G>A	p.Gly389Glu	missense	Exon 5 of 6	ENSP00000546193.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.07e-7 AC: 1 AN: 1414428 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 704652

African (AFR) AF: 0.00 AC: 0 AN: 30040

American (AMR) AF: 0.00 AC: 0 AN: 40968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25074

East Asian (EAS) AF: 0.00 AC: 0 AN: 34934

South Asian (SAS) AF: 0.00 AC: 0 AN: 84186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37894

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5644

European-Non Finnish (NFE) AF: 9.12e-7 AC: 1 AN: 1096926

Other (OTH) AF: 0.00 AC: 0 AN: 58762

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.69
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.053
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.020	D
Polyphen		0.50	P
Vest4		0.42
MutPred		0.23		Gain of solvent accessibility (P = 0.0074)
MVP		0.19
MPC		0.79
ClinPred		0.50	D
GERP RS		2.6
Varity_R		0.12
gMVP		0.33
Mutation Taster		=96/4	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: rs199701408; hg19: chr19-49106761;